Liver diseases are a global health issue with an annual mortality of 80,000 patients, mainly due to complications that arise during disease progression, as effective treatments are lacking. This study evaluated the hepatoprotective effects of two derivatives of cinnamic acid, LQM717 and LQM755, in a murine model of acute liver damage induced by carbon tetrachloride (CCl 4 g/kg, single dose p.o.). Male Wistar rats were pretreated with five doses of LQM717 (20 mg/kg i.p.) or LQM755 (equimolar dose), starting 2 days before inducing hepatotoxic damage with CCl. The key parameters of hepatocellular function and damage showed significant increases in ALT, ALP, GGT, and total and direct bilirubin in rats intoxicated with CCl, with decreased liver glycogen and serum albumin. Macroscopic and microscopic liver examinations revealed reduced inflammation, necrosis, and steatosis in animals pretreated with LQM717 or LQM755. Hepatomegaly was observed only in the LQM717 + CCl group. LQM755 statistically provided partial protection against increases in ALT and ALP and completely prevented elevations in GGT and total and direct bilirubin. LQM755 completely prevented albumin reduction, while LQM717 only partially prevented it. Both compounds partially prevented glycogen depletion. Bioinformatic analysis identified 32 potential liver protein targets for LQM717 and 36 for LQM755. These findings suggest that LQM717 and LQM755 have significant hepatoprotective effects against CCl-induced acute liver injury, providing information for future studies in other acute and chronic models, as well as to elucidate their mechanisms of action.