An experiment on assessing the differential response of Leptochloa chinensis and Echinochloa colona to the varying concentrations of broad-spectrum herbicide bispyribac-sodium (BS) was carried out in the midland laterites of Kerala. Seedlings of both weeds at 4-5 leaf stage were treated with 50, 100 and 200% field recommended dose (FRD) of bispyribac-sodium, 10 SC, PI Industries) 0.0125, 0.025 and 0.05 kg/ha, respectively. Differential response by weeds was evaluated using amino acid content estimation and protein profiling by Sodium Dodecyl Sulphate - Poly Acrylamide Gel Electrophoresis. The amino acid content of L. chinensis was not influenced by the increasing concentration of BS, whereas it was found to decrease with an increasing concentration of BS in E. colona. The parameters examined to evaluate the varying response, viz. protein content, number of proteins expressed and molecular weight of proteins shown higher values in L. chinensis compared to E. colona, irrespective of the concentration. However, increase in concentration of BS reduced the amino acid levels in E. colona. The reduced effectiveness of BS in inhibiting the biochemical processes associated with amino acid and protein synthesis in L. chinensis might explain its poor performance. The study verified the contrasting expression of amino acids and proteins in L. chinensis and E. colona, despite being from the same family. The study validated the need to identify suitable herbicides for broad spectrum weed management in direct seeded rice, especially when L. chinensis dominated the grass weed flora.