In this study, ionotropic gelation method was used for the preparation of ibuprofen-loaded calcium alginate (CALG) and ethylenediamine (EDA) treated calcium alginate (EDA-CALG) microspheres. The effect of EDA-treatment on drug entrapment efficiency, particle size, morphology, swelling behavior and in vitro release characteristics of the microspheres was investigated by varying its concentration from 0.5 to 2% (v/v). The reduction in drug entrapment efficiency by a maximum of 44.60% was noted for EDA-CALG microspheres compared to untreated CALG microspheres. The particle size and swelling index of EDA-CALG microspheres were reduced with increasing EDA concentration. All the microspheres were observed to retain their spherical shapes with rough surfaces. EDA-CALG microspheres prepared using 1% and 2% v/v EDA, released almost all of its content within 7 h in pH 6.8 phosphate buffer, however, CALG microspheres were found to release the same within 3 h. The intensity of melting endothermic peak of ibuprofen reduced significantly at lower drug load as experienced from DSC thermograms. The FT-IR spectrum of pure ibuprofen, ibuprofen-loaded CALG and EDA-CALG microspheres showed the characteristic band of C = O stretching vibration of ibuprofen. Hence, this study revealed that EDA can be employed for the preparation of ibuprofen-loaded CALG microspheres to retard the drug release to some extent.