Objective: To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies. Methods: The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation. The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation, membrane stabilization assays. The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays. The nitric oxide level was determined through Griess reagent. TNF-α and IL-6 levels were estimated using ELISA kits. In vivo studies were carried out in male Wistar rats through injection of Freund's adjuvant in the hind paw. Paw edema was measured through the Vernier scale and levels of alanine aminotransferase, aspartate transaminase, TNF-α, IL-6, and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment. GraphPad Prism6 was used for analyzing the results. Results: The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of (218.9±15.6) μg/mL and stabilized the membrane of red blood cells with an IC50 value of (275.9±19.1) μg/mL. The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20 μg/mL in MTT assays. The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies. Conclusions: The results indicate that the peptide/polypeptide fraction of Aloe vera has anti-inflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways. © 2019 Wolters Kluwer Medknow Publications. All rights reserved.