Totally Spies!

Framing each episode is a subplot that focuses on the girls' everyday lives as high school (and later university) students, dealing with relationships and their longtime high school nemesis Mandy.

Joly Herman of Common Sense Media gave the series a mixed review, rating the show 3 out of 5 stars and writing that "We think it's a decent show to catch once in a while, but anything more regular might give viewers the like, slightest headache." Joe Corey of Inside Pulse had a more positive review, calling the show "fun enough for small kids who want a Charlie's Angels undercover action show.

The trio does their best to balance the fun of being in the espionage game without it being too risky." Matt Hinrichs of DVD Talk gave a positive review, calling the action in the first three seasons "decently written enough for adults to enjoy." After four seasons, the show had reached over 130 countries and was met with enthusiasm among ages 6–11 that included both girls and boys, and had a Pokémon-like appeal to a broad range of age and gender.

In an interview before season three, David Michel said, "The one thing that surprised us the most is the consistency in the male / female viewership split: from Brazil to Italy, we have a 50% boys 50% girls audience ratio, whereas everybody was predicting the show would score very low on boys." Scott Stoute of ScreenRant listed the show among his "10 Girl Cartoons (That Guys Secretly Love)" list.

The Parents Television Council, in their March 2006 report, noted that the show did not contain offensive language, but expressed concern about the "nature of the violence of the show" in an episode where rats were released to psychologically torture Jerry and Clover, and the sexual content exampled by a sunblock ad by a bikini-clad woman.

In 2022, a writer for the Architectural Digest magazine praised Totally Spies! for its interior design choices and its "hyper Y2K, retro futuristic style".