Galactomannans are versatile macromolecules with broad industrial potential. The influence of changes in the chemical structures and respective bioactivities of these polysaccharides have been extensively studied. The derivatives obtained by sulfation, complexation, and phosphorylation are the most studied biological properties in galactomannans. The derivatives obtained have shown several pharmacological activities such as antiviral, antimicrobial, anticoagulant, fibrinolytic, chemopreventive, anticancer, antioxidant, chondroprotective, analgesic, immunomodulatory, and antileishmanial. Considering the relevance of these studies, we aim to provide an overview of studies that apply galactomannan modification or derivatization strategies to improve their properties for applications in the biomedical area. We identified the success of most modified galactomannans for pharmacological purposes. However, some studies found loss of bioactivity of the original polysaccharide after chemical changes to its original structures.