AbstractPhotodynamic therapy (PDT) is extensively explored for anticancer and antibacterial applications. It typically relies on oxygen‐dependent generation of reactive oxygen species (ROS) to realize its killing effect. This type of therapy modality shows compromised therapeutic results for treating hypoxic tumors or bacteria‐infected wounds. Recently, alkyl radicals attracted much attention as they can be generated from some azo‐based initiators only under mild heat stimulus without oxygen participation. Many nanocarriers or hydrogel systems have been developed to load and deliver these radical initiators to lesion sites for theranostics. These systems show good anticancer or antimicrobial effect in hypoxic environment and some of them possess specific imaging abilities providing precise guidance for treatment. This review summarizes the developed materials that aim at treating hypoxic cancer and bacteria‐infected wound by using this kind of oxygen‐irrelevant alkyl radicals. Based on the carrier components, these agents are divided into three groups: inorganic, organic, as well as inorganic and organic hybrid carrier‐based therapeutic systems. The construction of these agents and their specific advantages in biomedical field are highlighted. Finally, the existing problems and future promising development directions are discussed.