Abstract: In one aspect, the present disclosure provides targeted complement-activating molecules comprising a target-binding domain and a complement-activating serine protease effector domain. In some embodiments, the target-binding domain is derived from an antibody or an antigen-binding fragment thereof. Also provided are compositions and methods for treating cancer, autoimmune disease, or microbial infection, including bacterial, viral, fungal, or parasitic infection, using targeted complement-activating molecules.