A family of stable anticancer gold(III)-based therapeutic complexes containing cyclometalated triphenylphosphine sulfide ligands have been prepared. The anticancer properties of the newly developed complexes [AuCl2{κ2-2-C6H4P(S)Ph2}] (1), [Au(κ2-S2CNEt2){κ2-2-C6H4P(S)Ph2}]PF6 (2), [AuCl(dppe){κC-2-C6H4P(S)Ph2}]Cl (3), and [Au(dppe){κ2-2-C6H4P(S)Ph2}][PF6]2 (4) were investigated toward five human cancer cell lines [cervical (HeLa), lung (A549), prostate (PC3), fibrosarcoma (HT1080), and breast (MDA-MB-231)]. In vitro cytotoxicity studies revealed that compounds 2-4 displayed potent cell growth inhibition (IC50 values in the range of 0.17-2.50 μM), comparable to, or better than, clinically used cisplatin (0.63-6.35 μM). Preliminary mechanistic studies using HeLa cells indicate that the cytotoxic effects of the compounds involve apoptosis induction through ROS accumulation. Compound 2 also demonstrated significant inhibition of endothelial cell migration and tube formation in the angiogenesis process. Evaluation of the in vivo antitumor activity of compound 2 in nude mice bearing cervical cancer cell (HeLa) xenografts indicated significant tumor growth inhibition (55%) with 1 mg/kg dose (every 3 days) compared with the same dose of cisplatin (28%). These results demonstrate the potential of gold(III) complexes containing cyclometalated triphenylphosphine sulfide ligands as novel metal-based anticancer agents.