Mitochondria generate energy but malfunction in many cancer cells, hence targeting mitochondrial metabolism is a promising approach for cancer therapy. Here we have designed cyclometallated iridium(iii) complexes, containing one TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43H43N6O2Ir1·PF6]˙ (Ir-TEMPO1) and two TEMPO spin labels [C52H58N8O4Ir1·PF6]˙ (Ir-TEMPO2). Electron paramagnetic resonance (EPR) spectroscopy revealed spin-spin interactions between the TEMPO units inIr-TEMPO2. BothIr-TEMPO1andIr-TEMPO2showed bright luminescence with long lifetimes (ca.35-160 ns); whileIr-TEMPO1displayed monoexponential decay kinetics, the biexponential decays measured forIr-TEMPO2indicated the presence of more than one energetically-accessible conformation. This observation was further supported by density functional theory (DFT) calculations. The antiproliferative activity ofIr-TEMPO2towards a range of cancer cells was much greater than that ofIr-TEMPO1, and also the antioxidant activity ofIr-TEMPO2is much higher against A2780 ovarian cancer cells when compared withIr-TEMPO1. Most notablyIr-TEMPO2was particularly potent towards PC3 human prostate cancer cells (IC50= 0.53 μM), beingca.8× more active than the clinical drug cisplatin, andca.15× more selective towards cancer cellsversusnormal cells. Confocal microscopy showed that bothIr-TEMPO1andIr-TEMPO2localise in the mitochondria of cancer cells.