Hydrogels made of plant-derived biomass have gained popularity in biomedical applications because they are frequently affordable, readily available, and biocompatible. Finding the perfect plant-derived biomass-based hydrogels for biomedicine that can replicate essential characteristics of human tissues in regard to structure, function, and performance has proved to be difficult. In this review, we summarize some of the major contributions made to this topic, covering basic ideas and different biomass-based hydrogels made of cellulose, hemicellulose, and lignin. Also included is an in-depth discussion regarding the biosafety and toxicity assessments of biomass-based hydrogels. Finally, this review also highlights important scientific debates and major obstacles regarding biomass-based hydrogels for biomedical applications.