Mitochondria-targeted iridium complexes for anticancer studies have received increasing attention in recent years. Herein, three cyclometalated iridium(III) complexes Ir1-Ir3 [Ir(N^C)2(N^N)](PF6) (N^N = 2,2'-bipyridine (bpy)) or 2-(5-bromopyridin-2-yl)benzo[d]thiazole (bpybt); [N^C = 2-phenylpyridine (ppy) or 2-phenylquinoline (pq) or 2-(4-bromophenyl)benzo[d]thiazole (bpbt)] had been explored as potential mitochondria-targeted anticancer agents. All of the complexes mainly localized in the mitochondria and could be fixed on the mitochondria through a nucleophilic reaction with reactive mitochondrial proteins. Further studies revealed that these complexes showed high anticancer activity, induced mitochondrial depolarization, elevated intracellular reactive oxygen species (ROS) levels, restrained thioredoxin reductase (TrxR) activity, and inhibited the formation of tumor cell colonies and angiogenesis. Further mechanistic studies showed that complex Ir2 could markedly stimulate the activation of caspase-3, regulate the expression of Bax and KI67, and trigger apoptosis.