Camptothecin (CPT), a natural antineoplastic agent that was originally isolated from the bark and stem of Camptotheca acuminata, targets a wide range of cancers by inhibition of topoisomerase I during DNA replication. In this study, we investigated the use of cucurbit[7]uril (CB[7]) for molecular encapsulation of CPT and the associated benefits of such encapsulation of CPT on its anti-cancer activity, and side effects have been systemically evaluated both in vitro and in vivo. The cytotoxicity of the free CPT and complexed CPT (CPT@CB[7]) was examined by MTT assay using both a healthy liver cell line (L02) and a liver cancer cell line (Bel-7402). Interestingly, both the free CPT and CPT@CB[7] demonstrated comparable anti-cancer efficacy in vitro on the cancer cell line Bel-7402, whereas CPT@CB[7] showed obviously lower toxicity on the healthy liver cell line L02, in comparison with the free CPT. The anti-cancer/anti-angiogenic activity and non-specific toxicity of both free CPT and CPT@CB[7] were further investigated in vivo with both transgenic and wild-type zebrafish models, showing again that CPT@CB[7] exhibited reduced non-specific toxicities with well-preserved anti-angiogenic activities, when compared with the free CPT. These results demonstrate that CB[7] may work as a functional excipient for alleviation of undesired side-effects of selected organic drugs.