Cancer treatment has become one of the biggest challenges in modern medicine. Recently, many efforts have been devoted to treat tumors by surgical resection, radiotherapy, or chemotherapy. In comparison to these methods, photo-thermal therapy (PTT) with noninvasive, controllable, direct, and precise characteristics has received tremendous attention in eliminating tumor cells over the past decades. In particular, PTT based on biomacromolecule-based photo-thermal agents (PTAs) outperforms other systems with high photo-thermal efficiency, simple coating, and low immunogenicity. Considering the unique advantages of biomacromolecule-based PTAs in tumor treatment, it is necessary to summarize the recent progress in the field of biomacromolecule-based PTAs for tumor treatment. Herein, this minireview outlines recent progress in the fabrication and applications of biomacromolecule-based PTAs. Within this framework, various types of biomacromolecule-based PTAs are highlighted, including cell-based agents, protein-based agents, nucleotide-based agents, and polysaccharide-based PTAs. In each section, the functional design, photo-thermal effects, and potential clinical applications of each type of PTA are discussed. Finally, a brief perspective for the development of biomacromolecule-based PTAs is presented.