A facile and efficient methanesulfonic acid-catalyzed, solvent-free, microwave-assisted method was developed for the synthesis of biologically active 3,3-bis(hydroxyaryl)oxindoles and spirooxindoles bearing a xanthene moiety. The scope of the procedure was investigated with a wide range of isatin and phenol derivatives; moreover, the reaction mechanism was studied by density functional theory calculations. Both 3,3-bis(hydroxyaryl)oxindoles and spirooxindoles bearing a xanthene moiety synthesized were evaluated for their anticancer and antimicrobial activity, and most of them showed promising or significant activity on six cancer cell lines and against Gram-positive bacteria.