Pluchea indica (L.) Less leaves contain chlorogenic acid, which have antioxidant activity. This study aims to evaluate the ability to inhibit lipid peroxidation of P. indica leaf extract obtained from three natural deep eutectic solvents (NADES) based on choline chloride (ChCl). The chlorogenic acid content in the extracts was determined by RP-HPLC. Evaluation of lipid peroxidation inhibitory activity (LPOI) was carried out using the Thiobarbituric Acid Reactive Substances (TBARS) method on rat liver homogenates ex vivo. The study was carried out in silico against three enzymes, namely cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and cytochrome P450 (CYP450). The ChCl-Urea (1:2) extract of P. indica leaves contained the highest levels of chlorogenic acid (0.404%, w/w). The extract at 12.5% (v/v) gave the best LPOI activity with a percentage of inhibition of 22.5%. Chlorogenic acid as an antioxidant in inhibiting lipid peroxidation could be influenced by interaction with COX-2 and CYP450 inhibition in silico with binding energy values of −7.27 and −6.47 kcal/mol, respectively. Thus, chlorogenic acid, one of the active compounds from P. indica leaves, was responsible for inhibiting lipid peroxidation. However, in the future, it is necessary to investigate other phenolic chemical components from the NADES extract of P. indica leaves that play a role in this activity. Copyright © 2025 by Indonesian Journal of Pharmacy (IJP).