In this work, the Maillard reaction of polyglutamic acid (PGA) and glucose (Glc) was studied, and its functional, polymeric, and colored products were used to dye silk fiber with the aim of imparting bioactivities to silk. The UV–Vis spectroscopic analysis, which was employed to monitor the reaction, revealed the rapid formation of yellowish-brown products at pH 12 and 90 °C, and the great impact of glucose content on the quantity of the products. The FT-IR analysis validated the formation of melanoidin colorants. The silk fiber dyed with the PGA/Glc reaction products at pH 3 displayed a yellowish-brown color, and had very good wash and rub fastness, but poor light fastness. The incorporation of the UV-absorbing moiety into the PGA/Glc reaction products enhanced their light stability. The SEM analysis revealed that the dyed silk fiber was covered by polymeric substances. The dyed silk exhibited durable antibacterial activity against Staphylococcus aureus and Escherichia coli, and good antioxidant activity. This research expands the application field of the Maillard reaction and provides a novel and eco-friendly approach to prepare the colored and bioactive silk materials.