The invention discloses a comprehensive method for preparation of raffinose and gossypol from cottonseed meal. The method comprises the technological steps of: (1) extracting oil-extracted cottonseed meal with a polar solvent so as to obtain an extracted solution; (2) filtering the extracted solution, and removing an organic solvent in vacuum so as to obtain an aqueous phase and a solid phase; (3) subjecting the aqueous phase to filtration, flocculation, decoloration and desalination, decoloration, as well as desolventizing, thus obtaining raffinose; (4) first adding enzymes into the solid phase to carry out hydrolysis, then using an acid to adjust the solution to acidic, and performing precipitation and separation, thus obtaining a solid; (5) adding ether, halohydrocarbon, ester and/or low level ketone solvents to dissolve gossypol, and then filtering out impurities to obtain a gossypol-containing filtrate; and (6) subjecting the gossypol-containing filtrate to crystallization and crystal growing under nitrogen protection, then conducting filtration and drying, thus obtaining acicular crystals. The method can realize combined industrial production of dephenolized cottonseed protein, raffinose and gossypol, is suitable for large-scale production, and realizes comprehensive processing as well as maximum valuation of cottonseeds.