Anthropic diesel-derived contamination of Mediterranean coastal waters is of great concern. Nature-based solutions such as phytoremediation are considered promising technologies to remove contaminants from marine environments. The aim of this work was to investigate the tolerance of the Mediterranean autochthonous seaweed Caulerpa prolifera (Forsskal) Lamouroux to diesel fuel and its hydrocarbon degradation potential. Changes in C. prolifera traits, including its associated bacterial community abundance and structure, were determined by fluorescence microscopy and next-generation sequencing techniques. Thalli of C. prolifera artificially exposed to increasing concentration of diesel fuel for 30 days and thalli collected from three natural sites with different levels of seawater diesel-derived hydrocarbons were analysed. Gas chromatography was applied to determine the seaweed hydrocarbon degradation potential. Overall, in controlled conditions the lower concentration of diesel (0.01%) did not affect C. prolifera survival and growth, whereas the higher concentration (1%) resulted in high mortality and blade damages. Similarly, only natural thalli, collected at the most polluted marine site (750 mg L−1), were damaged. A higher abundance of epiphytic bacteria, with a higher relative abundance of Vibrio bacteria, was positively correlated to the health status of the seaweed as well as to its diesel-degradation ability. In conclusion, C. prolifera tolerated and degraded moderate concentrations of seawater diesel-derived compounds, especially changing the abundance and community structure of its bacterial coating. The protection and exploitation of this autochthonous natural seaweed-bacteria symbiosis represents a useful strategy to mitigate the hydrocarbon contamination in moderate polluted Mediterranean costal environments.