A series of bischalcones was synthesized and screened for their effect on acid and alkaline phosphatases. In addition, molecular modeling and docking of these compounds into alkaline phosphatase using iGemdock was performed in order to predict the affinity and orientation of the designed compounds at the active site and was compared with the established inhibitor levamisole. The iGemdock docking fitness resulted in decrease in total energy (ranging from -75.50 to -100.84) for all the synthesized compounds which were less than levamisole (-50.69) revealing higher binding with the enzyme. The compounds were synthesized by Clasien–Schimdt condensation and their effect was observed on the activity of acid and alkaline phosphatases. The results showed that synthesized bischalcones were inhibitory to alkaline phosphatases, whereas an activating effect was observed on the activity of acid phosphatase. The type of inhibition and Ki values of bischalcones on alkaline phosphatase were also determined.