[8] The series follows the adventures of grade school kid incarnations of Peter Parker / Spidey, Miles Morales / Spin and Gwen Stacy / Ghost-Spider as they fight villains such as Rhino,[9] Doc Ock, Green Goblin, Electro, Black Cat, Sandman, Zola, Lizard, and Trapster.

Spidey, Spin, and Ghost-Spider would sometimes receive aid from other superheroes such as Black Panther, Ms. Marvel, her dog Lockjaw, Hulk, Iron Man, Ant-Man, Wasp, Reptil, Thing, his partner H.E.R.B.I.E., Squirrel Girl, her sidekick Tippy-Toe, White Tiger, Moon Girl and her partner Devil Dinosaur.

[8] Patrick Stump of the pop punk rock band Fall Out Boy wrote, composed, and performed the theme song for the series.

[4][5] On October 10, 2022, it debuted on CBeebies in the United Kingdom, making this the first show based on a Disney property to premiere on said network.

[7] Adam Levine of Looper ranked Spidey and His Amazing Friends 19th in their "Every 2021 Superhero Movie And TV Show Ranked" list, asserting, "Bright, colorful, and wonderfully animated, it doesn't get high marks from comic book diehards, but has been nonetheless well-reviewed by parents of its young target audience for its wholesome stories and message of teamwork.

"[62] Marisa Lascala of Good Housekeeping included Spidey and His Amazing Friends in their "60 Best Kids' TV Shows and Family Series of All Time" list.

This modern update of the classic 80's cartoon left out Iceman and Firestar, and traded them with other popular web-slingers like Ghost-Spider/Gwen Stacy and Miles Morales, nicknamed 'Spin' to avoid confusion with Peter Parker's alter ego.