Aspirin and diclofenac conjugates with dextran were synthesized as potential macromolecular prodrugs under homogeneous reaction conditions by using 4-methyl-benzenesulfonyl chloride as an acylating agent in the presence of triethylamine as a base. Highly pure conjugates with good yields were synthesized by this acylation method. All of the products were found soluble in aqueous medium as well as in dimethylsulfoxide and N,N-dimethylacetamide. The UV/Vis spectrophotometry has indicated the incorporation of drugs in conjugates and extent of substitution of drug onto dextran polymer. Covalent attachment of the drug onto the drug carrier polymer (dextran) was verified by (1)H NMR and Fourier transform infrared (FTIR) spectroscopic analysis. The prodrugs were analysed by powder X-ray diffraction (XRD) measurements. Phase changes were noticed by powder XRD for all macromolecular prodrugs indicating the change of state of matter towards more crystallinity. Therefore, fabricated macromolecular prodrugs are potential candidates to show better pharmacokinetic profile. All of the products were thoroughly characterized by using different spectroscopic techniques.