Background: In different parts of the world, citrus fruit peels are considered potential sources for natural anti-inflammatory agents. The present study was designed to evaluate the anti-inflammatory potential of Citrus. sinensis fruit peel in search for a natural alternative medicine. Methods: In vitro inflammation was modeled through egg albumin denaturation, human erythrocyte membrane destabilization- in hypotonic and thermal conditions; treated with the aqueous peel extract at various concentrations - 31.25, 62.5, 125, 250 and 500 μg/ml and compared with the same concentrations of the reference acetyl salicylic acid (ASA). Half maximal inhibitory concentration (IC50) was determined from the dose-response curve. In addition, phytochemical and physicochemical properties were also assessed. Results: In all experiments, IC50 of the test sample was achieved at higher concentrations (>200 μg/ml). However, in hypotonic and hyperthermic conditions, IC50 was attained at much higher concentrations (>250 μg/ml). ASA showed greater responses in inhibition in comparison to that of the sample. The qualitative phytochemical analysis exhibited that the aqueous extract contained protective components like tannin, phenol, flavonoid, reducing sugar, protein, carbohydrate and steroid. Conclusion: The demonstration of anti-protein denaturation and erythrocyte membrane stabilization indicated a significant potential of the aqueous fruit peel extract as natural anti-inflammatory agent which generated the context for further in-depth investigation.