Introduction: Psoriasis is an immune-mediated chronic, inflammatory skin disease characterized by hyper proliferative keratinocytes and their infiltration into the dermis of T cells, dendritic cells, macrophages and neutrophils. There is ample evidence suggesting the key role of dysregulation of immune cells in the skin, particularly T cells, in the pathogenesis of psoriasis. Calcineurin, a calcium and calmodulin dependent serine/threonine protein phosphatase plays a major role in increasing the production of T cells and thus in the development of psoriasis. Flavonoids such as quercetin and kaempferol are known to inhibit development of psoriasis. Objective: We have performed docking of novel designed flavonoid analogues of quercetin and kaempferol to Calcineurin by insilicoanalysis to predict their potential as antipsoriatic candidates. Materials: Eighty analogues each of quercetin and kaempferol were designed using Schr__ampersandsignouml;dinger- Maestro 11 and docked with Calcineurin using PyRx software. Results: The best binding affinities (kcal/mol) were predicted for5 quercetin analogues- Q79 (-6.1), Q78, Q77 andQ76 (-5.9) and Q44 (-4.8) and5 kaempferol analogues-K18, K40 andK44 (-7.6), K3, K48 (-7.5). Conclusion: This study using PyRx software strongly supports the importance of computational approach in drug discovery. The short listed novel analogues of quercetin and kaempferol follow Lipinski rule of 5, satisfying basic parameters for drug likeliness. QSAR and pharmacokinetic analysis can be deployed in future, to further characterize them. Eventually, most promising analogues can be synthesized and evaluated to verify their actual antipsoriatic activity.