Doxorubicin (Dox) is a highly effective anticancer agent, but eventually induces cardiotoxicity associated with increased production of reactive oxygen species (ROS). We previously reported that the formation of protein complex between transient receptor potential canonical 3 (TRPC3) and NADPH oxidase 2 (Nox2) mediates Dox-induced cardiac atrophy in mice. The aim of this study was to identify a drug already approved for clinical use that blocks Dox-induced cytotoxicity, and demonstrate whether inhibition of TRPC3-Nox2 complex by this drug attenuates Dox-induced systemic tissue wasting in mice. Drug screening was performed using Raw264.7 macrophage cell line. We investigated whether inhibition of TRPC3-Nox2 complex contributed to attenuation of Dox-induced cytotoxicity, by measuring Nox2 protein stability through interaction between TRPC3 and Nox2. We found that ibudilast, an anti-asthmatic drug, attenuated the cytotoxicity induced by Dox and cisplatin, by inhibiting TRPC3-Nox2 functional interaction without reducing TRPC3 channel activity. These results identify a common mechanism underlying induction of systemic tissue wasting by Dox and a drug that could be repurposed to reduce the risk of cardiotoxicity by anti-cancer drugs.