The interaction of calf thymus DNA (CT DNA) and water‐soluble manganese corrole, 5,10,15‐tris(4‐carboxyphenyl)corrolatomanganese(III) (MnIIITCPC) has been studied by absorption spectra, fluorescence spectra and CD spectra, as well as by viscosity measurements. Results revealed that this manganese corrole binds to CT DNA via an outside groove binding mode with intrinsic binding constant Kb of 4.67×104 L·mol−1. DNA cleavage activities of MnIIITCPC in the presence of various oxidants were also investigated. MnIIITCPC can cleave the supercoiled plasmid pBR322 DNA to both nicked and linear form in the presence of hydrogen peroxide or tert‐BuOOH, while no nuclease activity was observed by using KHSO5 as oxidant. Inhibitor tests revealed that hydroxyl radicals or singlet oxygen was not involved in MnIIITCPC mediated DNA oxidative cleavage. It is suggested that (oxo)manganese(V) corrole is the possibly active intermediate in this oxidative cleavage reactions.