Lichen-derived Phenolic parietin (PNT) demonstrates promising anti-inflammatory and antioxidant properties with potential applications as a therapeutic agent. This study investigates, for the first time, the protective effects of PNT against obesity-induced inflammation, type 2 diabetes, oxidative stress, and tissues damages. In vitro and in silico analyses revealed strong interactions of PNT with key enzymes such as lipase, α-amylase, myeloperoxidase (MPO), phospholipase A2 (PLA2), 5-lipoxygenase (5-LO), and elastase (ELA), supported by favorable binding energies and low IC50 values. In obese rats, PNT at a dose of 100 mg/kg bw significantly reduced α-amylase and lipase activities, leading to a 19 % decrease in body weight, a 42 % reduction in blood glucose levels, and a 112 % increase in liver glycogen content, as well as oral glucose tolerance test (OGTT). Furthermore, this pigment prevents the dysregulation of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and total lipids (TL) levels in tissues and serum. PNT also suppressed immune cell infiltrationin the pancreas evidenced by histological analysis and reductions in MPO activity (and inflammatory enzyme activity (PLA2, 5-LO, and ELA). Additionally, PNT reduced stress oxidant level, as shown by decreased hydrogen peroxide (H ₂ O ₂ ), thiobarbituric acid reactive substances (TBARS), and total oxidant status (TOS), while enhancing total antioxidant status (TAS). Histological analysis confirmed reduced necrosis and neutrophil infiltration in the pancreas, of PNT-treated rats. These findings highlight the potent anti-inflammatory and antioxidant properties of PNT, offering therapeutic potential for mitigating tissue damage and improving organ function in obesity and type 2 diabetes.