Photodynamic therapy (PDT) is an emerging treatment modality for combating pathogenic infections and cancer diseases by utilizing light-sensitive agents, known as photosensitizers (PS), to generate reactive oxygen species (ROS) upon exposure to light. Among various PS, indocyanine green (ICG) stands out due to its FDA approval for clinical use and its dual capacity for both photothermal and photodynamic actions. Commonly utilized primarily for imaging, ICG has demonstrated significant potential in antimicrobial PDT, particularly due to its ability to generate singlet oxygen, the key intermediate product in pathogen inactivation. The absorption of near-infrared (NIR) light, which can penetrate deeper tissues, by ICG also enables effective targeting of infections at deeper sites of the biological tissue. While ICG’s anionic nature limits its direct interaction with bacterial cells, especially gram-negative bacteria, recent advances suggest that this limitation can be overcome by incorporating ICG into cationic nano-/biomaterials. These strategies enhance the interaction between ICG and pathogens, improving the efficiency of PDT. Additionally, combining ICG-mediated PDT with photothermal therapy (PTT) facilitates both ROS production and heat generation mechanisms simultaneously, further enhancing antimicrobial efficacy. These integrated approaches have shown promising results in animal models, effectively eradicating infections, accelerating wound healing, and reducing the required ICG doses. Consequently, ICG-mediated PDT holds significant promise as an alternative to conventional antimicrobial treatments, particularly in the face of rising drug resistance. With continued optimization and integration of ICG into nano/biomaterials, this therapy could play a key role in the future of infection management, offering a multifaceted approach to treating resistant pathogens while minimizing side effects on healthy tissues.