Abstract Infectious diseases (such as wound infections) caused by pathogenic microorganisms can lead to serious consequences and even threaten life. The emergence of drug‐resistant bacteria has severely prevented the validity of traditional antibiotics. Therefore, developing novel antimicrobial strategies without drug‐resistant holds great promise for maximizing efficacy and minimizing the risk of drug‐resistance of resistant bacterial infections. Herein, near‐infrared (NIR)‐absorbing A–D–A type conjugated oligomers with a tunable backbone are designed and synthesized for regulating their photothermal conversion. After being assembled into nanoparticles, the conjugated oligomer CP‐F8P nanoparticles (NPs) containing a strong electron‐donating component show the strongest photothermal conversion efficiency of 81.6%. The low concentration of CP‐F8P NPs receive over 99% of antimicrobial efficiency against Amp r E. coli , S. aureus , and C. albicans upon NIR irradiation, and the phototherapy treatment of CP‐F8P NPs can effectively promote wound healing in diabetic mice with good biocompatibility. This work provides ideas for the design of efficient NIR‐activated antimicrobial reagents against drug‐resistant microbial infections.