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Mercury (Hg) is a pollutant that has toxic effects on ecosystems and biota. As it biomagnifies in the food chain, its presence in edible fish poses a high risk to human health. Herein, total Hg (THg) content was quantified in 2018–2019 using thermal decomposition amalgamation atomic absorption spectrometry in muscle tissue of red mullet (Mullus barbatus), a commercially important species throughout the Adriatic Sea (Central Mediterranean Sea). Specimens were grouped into 16 pools based on sex, reproductive stages, and sampling area. The overall mean value of THg content was 0.20 ± 0.15 mg kg−1 in terms of wet weight. THg levels in males and females showed no statistically significant differences, whereas specimens that were captured in open sea showed a higher THg content than coastal samples. Statistically significant differences between THg content and the reproductive stages of fish were found in females. However, neither lipid content nor fish length were statistically correlated with THg content. The analyzed specimens were considered to be safe food according to EU directives, but it is necessary to exercise caution and further investigate Italian people in the 0–18 age group, because they were found to be exposed to a higher dose of methylmercury than the safety threshold set by the EFSA.