Biological metal-organic frameworks (bio-MOFs) constitute a growing subclass of MOFs composed of metals and bio-ligands derived from biology, such as nucleobases, peptides, saccharides, and amino acids. Bio-ligands are more abundant than other traditional organic ligands, providing multiple coordination sites for MOFs. However, bio-MOFs are typically prepared using hazardous or harmful solvents or reagents, as well as laborious processes that do not conform to environmentally friendly standards. To improve biocompatibility and biosafety, eco-friendly synthesis and functionalization techniques should be employed with mild conditions and safer materials, aiming to reduce or avoid the use of toxic and hazardous chemical agents. Recently, bio-MOF applications have gained importance in some research areas, including imaging, tumor therapy, and targeted drug delivery, owing to their flexibility, low steric hindrances, low toxicity, remarkable biocompatibility, surface property refining, and degradability. This has led to an exponential increase in research on these materials. This paper provides a comprehensive review of updated strategies for the synthesis of environmentally friendly bio-MOFs, as well as an examination of the current progress and accomplishments in green-synthesized bio-MOFs for drug delivery aims and tumor treatments. In conclusion, we consider the challenges of applying bio-MOFs for biomedical applications and clarify the possible research orientation that can lead to highly efficient therapeutic outcomes.