Background and aim <p>Although it has been shown that coffee consumption can prevent the development of hepatic fibrosis and cirrhosis; the role of caffeine in improvement of cirrhosis, and its complications has not yet been elucidated.</p> Methods <p>In the present randomized placebo-controlled clinical trial, fifty patients with more than 6 months of cirrhosis diagnosis were recruited. Patients were randomly assigned to receive either two caffeine tablets (each 200&#xa0;mg), or placebo for 8 weeks. Both participants and investigators were blinded to the randomization groups. Serum concentration of lipid profile, anthropometric measurements, handgrip strength, and dietary intakes were assessed at the baseline and the end of the intervention.</p> Results <p>In the caffeine group, handgrip strength (4.7 ± 3.2&#xa0;kg) and MELD score (-3.87 ± 3.3) were improved, significantly more than control group (0.56 ± 3.1&#xa0;kg <i>P</i> = 0.006, -1.14 ± 4.1 <i>P</i> = 0.043, respectively) after adjusting for baseline values. Although triglyceride, total cholesterol and LDL-C increased in the caffeine group and decreased in the control group, no significant differences were detected in lipid profile between two groups after 8 weeks. Also, there were no significant differences in dietary intakes within and between groups (<i>P</i> &gt; 0.05).</p> Conclusion <p>It can be concluded that supplementation with 400&#xa0;mg caffeine daily for 8 weeks in patients with cirrhosis may result in improvement of handgrip strength with no significant effect on lipid profile. Further studies with different caffeine dosages, and study duration are needed to find the optimum dosage of supplementation.</p> Trial registration <p>This trial was registered at the Iranian Registry of Clinical Trials (Registration ID: IRCT20100524004010N34) on 08/07/2022.</p>