Quantitative structure-activity relationships (QSAR) analyses have been attempted on a new set of 4-oxothiazolidines and 5-arylidines derivatives using linear free energy related (LFER) model of Hansch to explain the structural requirements for lipoxygenase inhibition. The QSAR study showed that successful correlation can be achieved for inhibitory activity of 4-oxothiazolidines and 5-arylidines (R>0.9, Q2>0.7). The result of the QSAR study suggests the bulky substituents in the thiazolidine nucleus will decrease the binding affinity of 4-oxothiazolidines derivatives towards lipoxygenase indicated by negative contribution of molar refractivity and connolly accessible area. The positive contribution of topological parameters (BI, MTI, CC and TVC) illustrates that increase in branching and presence of heteroatom is favorable for lipoxygenase inhibitory activity.