Background: An inflammatory, prevalent, and chronic skin disease is psoriasis. The term "classic skin lesions" refers to the erythematous, scaly, and well-defined plaques that are frequently located on the extensor surfaces. There have also been several psoriasis variations reported, such as the guttate, erythrodermic, pustular, and palmoplantar types. Psoriasis is typically diagnosed clinically, although distinctive histologic findings include a lymphocytic infiltration, dilated blood vessels, and hyper- and parakeratosis of the epidermis. Although the exact cause of psoriasis is unknown, genetic and environmental factors have been linked to the immune-mediated disease. Many health advantages are associated with flavonoids, such as their antiviral, anticancer, and antioxidant qualities. They also have cardio- and neuroprotective properties. The kind of flavonoid, its (potential) method of action, and its bioavailability all affect these biological functions. These reasonably priced pharmaceutical ingredients contain substantial biological activities and have been shown to be beneficial for a range of illnesses. Purpose: The present study was conducted to evaluate the efficacy of new flavonoid derivatives for their anti-psoriatic potential. Methodology: The scientific validation of the present work was conducted using a computational molecular docking analysis of the lead compounds luteolin, baicalein, and myricetin against the PDE4 enzyme. Result: The results of the current analysis indicate that the selected lead compounds are efficient anti-psoriatic agents, demonstrating binding affinities to the target protein PDE4 with binding energies of -7.269, -7.16, and -6.64 kcal/mol for baicalein, luteolin, and myricetin, respectively. Conclusion: The results demonstrated that each chosen lead compound for further study exhibited substantial inhibitory efficacy against PDE4, hence indicating its potential as an anti-psoriatic drug.