In the current study, we have examined the potential of Physostigmine and Harmaline, two natural alkaloids of significant importance, as inhibitors of DPP-IV. An extensive analysis of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds was conducted. Subsequently, molecular docking studies were performed to investigate the binding inhibitory potential of these compounds with the DPP-IV enzyme. The observation revealed that both compounds exhibited the ability to form conventional hydrogen bonds with the DPP-IV enzyme, suggesting their potential as inhibitors of the enzyme. By employing the strategy of synthesizing diverse semisynthetic derivatives, it is plausible to enhance the efficacy of DPP-IV inhibitors. Given that both of these molecules exhibit a range of drug-like properties, it is reasonable to consider their potential for further development