Response surface methodology was applied to optimize the microwave-assisted graft co-polymerization of acrylamide on Mimosa pudica seed mucilage. The effect of variables, microwave power and time of exposure, concentrations of acrylamide, mucilage and ammonium persulfate on grafting efficiency of graft co-polymerization was screened using Plackett-Burman experimental design. The results revealed that the concentration of acrylamide and mucilage are the most significant variables, which were further optimized using, a central composite design. A second-order polynomial equation fitted to the data was used to predict the response in the optimal region. The optimal grafting parameters provided graft co-polymer with grafting efficiency close to the predicted values. The proposed mathematical model is found to be robust and accurate for graft co-polymerization of acrylamide and Mimosa mucilage consistent with goals of maximizing grafting efficiency. The results of FT-IR, DSC, XRD, and SEM studies confirmed the formation of graft co-polymer of acrylamide and Mimosa mucilage.