mTOR (mammalian target of rapamycin) is an enzyme protein involved in intracellular signal transduction. It is known to constitute the mTOR pathway with many molecules and control important functions related to cell survival such as cell division, growth, metabolism and autophagy. Rapamycin and its derivatives are immunosuppressor macrolides that inhibit mTOR function and yield anti-proliferative activity in various malignancies. We screened for antibiotics that inhibit mTOR as therapeutic drug candidates and examined the effect of the drug. Clindamycin (CLDM), belonging to macrolides, inhibited survival and proliferation in human-derived glioma cell lines (U251, T98G, LN-229). CLDM also sensitized the antitumor effects of temozolomide. CLDM suppressed the phosphorylation of S6 protein and p70S6 Kinase in a dose-dependent manner. In NGT-41, a cell line derived from autopsy of an epithelioid glioblastoma patient, CLDM induced G1-S cell cycle delay and apoptosis. These results suggest that CLDM regulates the mTOR signaling as an intracellular communicator in glioma and controls tumor growth. We discuss the current and future applications of CLDM and related translational research possibly leading to novel therapeutic strategies against malignant glioma.