The emergence of drug-resistant bacteria is considered a critical public health problem. The need to establish alternative approaches to countering resistant microorganisms is unquestionable in overcoming this problem. Among emerging alternatives, antimicrobial photodynamic therapy (aPDT) has become promising to control infectious diseases. aPDT is based on the activation of a photosensitizer (PS) by a particular wavelength of light followed by generation of the reactive oxygen. These interactions result in the production of reactive oxygen species, which are lethal to bacteria. Several types of research have shown that aPDT has been successfully studied in in vitro, in vivo, and randomized clinical trials (RCT). Considering the lack of reviews of RCTs studies with aPDT applied in bacteria in the literature, we performed a systematic review of aPDT randomized clinical trials for the treatment of bacteria-related diseases. According to the literature published from 2008 to 2022, the RCT study of aPDT was mostly performed for periodontal disease, followed by halitosis, dental infection, peri-implantitis, oral decontamination, and skin ulcers. A variety of PSs, light sources, and protocols were efficiently used, and the treatment did not cause any side effects for the individuals.