Cuddles and Giggles are considered to be great friends and have had a few romantic experiences with each other throughout the series. Many fans consider them to have a boyfriend-girlfriend relationship (although Giggles is still seen with others in Love Bites - see the Trivia section below).
Cuddles is shown to be great friends with Giggles in many cases, in Blast from the Past, they skip along to the park along with Toothy and Lumpy; in This Is Your Knife, they are seen camping together along with Flaky and later Flippy; sat at a table together in Flippin' Burgers; in Class Act, they acted together in a play; in From Hero to Eternity, they had a snowball fight against each other; in Snow Place to Go, they were seen tanning next to each other; and at the beginning of Double Whammy Part I, they are seen riding a rollercoaster together and we’re riding on an elevator together in See You Later, Elevator. In We're Scrooged!, when Cuddles found that Toothy’s severed finger is fun to play with, he immediately went over to Giggles to play with it with her. He also pushed her on the swing in I Nub You. Cuddles was also one of the tree friends who volunteered to help build Giggles new house in Home Is Where the Hurt Is.
Cuddles has been shown in a few episodes to have romantic feelings for Giggles. Most notably, he spends the entirety of The Carpal Tunnel of Love of love attempting to woe her in numerous ways. They also shared a kiss in a reference to Lady and the Tramp as zombies in Remains to be Seen.
Though he is a much better friend to Giggles than he is to Flaky, the relationship is not perfect. In YouTube 101: Subscriptions, he is shown to take these feelings too far by covering his walls with her pictures as well as kissing one of her pictures on his desk, stalking her YouTube account, and going into an angry and emotional break down when he thought she was on a date with Disco Bear. In Class Act, he also had almost no reaction to her face getting sliced off. He also automatically assumed Giggles was going to miss her throw in From Hero to Eternity and laughs based on this assumption.
Though traditionally seen with Petunia, Giggles is likewise shown to be good friends with Cuddles, moreso than any of the other male characters. They are even seen playing on the swings together in the intro to the TV series. She becomes extremely distressed when she accidentally injures Cuddles in From Hero to Eternity immediately calling for help. She can also be seen mourning his grave in Happy Trails Pt. 2: Jumping the Shark. They also showed a very playful relationship in Flippin' Burgers when she laughed when he accidentally squirted her with ketchup instead of getting mad.
She has also shown occasional romantic feelings on rare occasions. In The Carpal Tunnel of Love, she is shown to be very moved by Cuddles’ romantic advances despite the failures and had almost kissed him twice. She is also seen happily walking hand-in-hand with him in I Nub You though this is not an exclusively romantic gesture.
The only mark against her opinion of Cuddles is that Giggles has been seen dating and/or displaying romatic interest towards other characters including: Russell, The Mole, Splendid, Cro-Marmot, Lumpy, Flippy, and Mime. However, it has been confirmed that her and Cuddles are only used as a couple on an episode basis and are not an official couple, meaning that Giggles has a right to date whoever she wants.
- This is the most popular pairing in the canon universe, along with the Handy-Petunia Relationship, but it is second or third most popular pairing in the fandom, as the Flippy-Flaky Relationship is the most popular couple among the fans.
- Giggles has also dated Russell three times (Sea of Love,You're Kraken Me Up, Put Your Back Into It), Cro-Marmot once (Cold Hearted), The Mole twice (Blind Date, Cold Hearted) and Flippy once (On My Mind). However, Cuddles may not be aware that she is dating other characters (as in YouTube 101: Subscriptions, he grows jealous when he thinks that Giggles is dating Disco Bear). This could mean that Giggles is cheating on Cuddles, that the aformentioned episodes take place in alternate universes, or that they take place before the two form their relationship.
- Cuddles and Giggles have one game each where they are the only playable character and are flying. Giggles is in Strandead and Cuddles in Hare Trigger.
- Within the series, they have so far only kissed when they were dead.
- They, along with Toothy and Lumpy, make up the four primary characters of Happy Tree Friends.