Introduction: Viral diseases are a current concern around the world. Treatment alternatives are a field of growing interest in treating these diseases. Curcumin has already proven effective and is known for its anti-inflammatory properties in vitro; however, the impact of this natural compound in the clinical setting needs to be clarified, especially in the use of COVID-19 disease. Methods: A systematic search was conducted in PubMed using MeSH terms in August 2023. All selected articles were randomized clinical trials that evaluated the anti-inflammatory effect of curcumin in patients with acute-stage COVID-19 viral diseases in people over 18 years of age. The research was conducted using MeSH terms. Results: 413 studies were identified, of which only 4 met the inclusion criteria. It was shown that curcumin reduces inflammatory markers in patients with COVID-19 in the acute phase. Discussion: Despite evidence of improvement of inflammatory markers of curcumin in subjects with COVID-19, the clinical utility is still unknown because most trials did not describe clinical outcomes. Conclusion: Although curcumin is a promising anti-inflammatory resource, more stringent clinical trials with well-defined results are needed to evaluate the effect of curcumin on clinical outcomes—additionally, strict protocols to control bias.