A girl named Ichigo Momomiya, and four other girls, Mint Aizawa, Lettuce Midorikawa, Pudding Fong, and Zakuro Fujiwara, have their DNA mysteriously combined with the DNA of endangered species. Gaining special abilities and a different appearance, they later find out that they have been chosen to protect Earth from a group of aliens (whose race is not named in Tokyo Mew Mew) who wish to 'reclaim it': Kish, Tart, Pie, and the mysterious Deep Blue, who have the power to control aliens which infect animals (infusors/Parapara), turning their hosts into monsters called Chimera Animals.
At the same time, these five girls must also work at the Café Mew Mew as waitresses, which is secretly the headquarters of Tokyo Mew Mew, owned by Ryou Shirogane, and Keiichiro Akasaka. To make things more difficult for Ichigo since she is mainly doing all the work at Café Mew Mew, she must also deal with finding out whether her crush, and later in the manga/anime boyfriend, Masaya Aoyama, likes her or knows that she is a Mew Mew. She is also pursued by two other boys, Ryou Shirogane and the alien Kish. Ichigo is only troubled for a part of the series however, for she finds out that Masaya does indeed have feelings for her and they become inseparable by series end.