Inflammation is pivotal in the pathogenesis and progression of the most challenging diseases and even cancer. Nanomedicine‐based strategy can be referred as a distinct solution to this complicated clinical obstacle by proposing an elaborated combination of effective therapeutic performances on inflammation and cancer. Herein, 2,2,6,6‐tetramethylpiperidine‐1‐oxyl doped polydopamine nanoparticles, termed as TPDA NPs, with the significantly improved reactive oxygen/nitrogen species (RO/NSs) scavenging performance and enhanced photothermal efficiency are designed and synthesized by constructing donor‐acceptor pairs, for prostate diseases treatment including anti‐inflammation and anti‐tumor. Benefiting from mimicking multi‐natural enzymes, including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase, TPDA NPs can inhibit the NF‐κB signaling pathways by downregulating the CD36 expression for the treatment of oxidative stress‐induced prostatitis. Especially, TPDA NPs can improve the prostatitis‐associated impairment of sexual behavior. By virtue of the enhanced photothermal‐conversion efficiency, TPDA NPs ablate prostate cancer and simultaneously decrease inflammatory reaction. Therefore, this work provides a “three birds with one shot” paradigm to utilize rationally designed TPDA NPs for efficient management of prostate diseases.