Iron is an essential metal for normal cellular physiology, but excess iron results in cell injury; it reacts with superoxide anions (O₂) and hydrogen peroxide (H₂O₂) to produce the hydroxyl radical (OH) and other reactive oxygen species (ROS) which can cause damage to body cells. Free radical damage can be prevented by food rich in antioxidants such as fruit and vegetables. In the present study, the ability of aqueous extracts of ripe (red) and unripe (green) hot peppers [Capsicum annuum, Tepin (CAT) and Capsicum chinese, Habanero (CCH)] (3.3–16.7 mg/ml) to prevent 25 μM Fe²⁺-induced lipid peroxidation in Rat’s brain (In vitro) were assessed using TBARS (Thiobarbituric acid reactive species). The total phenol and vitamin C content, as well as Fe²⁺-chelating ability, and the ability of the pepper extracts to prevent Fe²⁺/H₂O₂-induced decomposition of deoxyribose was also determined. The results of the study revealed that incubating the brain tissues in the presence of 25 μM Fe²⁺ caused a significant increase (p < 0.05) in MDA (Malondialdehyde) production in the rat’s brain (260%) when compared with the basal (100%). However, the pepper extracts (unripe and ripe) caused a significant decrease (p < 0.05) in the MDA production in both the basal and the Fe²⁺-induced lipid peroxidation in the Rat’s brain. However, CAT [ripe and unripe] had a significantly (p < 0.05) higher inhibitory effect on both basal and Fe²⁺-induced lipid peroxidation in the brain tissues than that of CCH (ripe and unripe). In addition, CAT (ripe and unripe) had a significantly higher (p < 0.05) total phenol, vitamin C and Fe²⁺ chelating ability than CCH (ripe and unripe). The unripe CAT had a significantly (p < 0.05) higher total phenol, Fe²⁺ chelating ability and inhibitory effect on the basal and Fe²⁺-induced lipid peroxidation in the brain tissues than the ripe pepper, while the reverse is the case with CCH where the red pepper had a higher values for the same parameters. However, ripe CAT and CCH had a significantly higher (p < 0.05) vitamin C content than the unripe; meanwhile both ripe and unripe peppers (CAT&CCH) did not significantly inhibit (p < 0.05) Fe²⁺/H₂O₂-induced decomposition of deoxyribose (Fenton reaction). The inhibitory effect of the pepper on lipid peroxidation (basal and Fe²⁺ induced) and Fe²⁺ chelating effect of the extracts were dose dependent. It was therefore concluded that hot peppers prevent Fe²⁺-induced lipid peroxidation, however CAT (ripe and unripe) are more potent inhibitors of Fe²⁺-induced lipid peroxidation than CCH (unripe and ripe), meanwhile unripe CAT had the highest protective ability and this is probably due to its higher total phenol content and Fe²⁺ chelating ability.