Characterization of a New Biocomposite Based on Bioactive Compounds from Ganoderma lucidum and Jellyfish Collagen Destined for In Vitro Evaluation of Antitumor Effects in the Oral Cavity

<b>Background/Objectives:</b> Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to treatment-related toxicity and impaired oral tissue regeneration. This study aimed to develop and characterize a novel biocomposite based on bioactive compounds from <i>Ganoderma lucidum</i> incorporated into marine collagen derived from <i>Rhizostoma pulmo</i> and to evaluate its physicochemical properties, antioxidant and antimicrobial activities, and in vitro antitumor potential in the oral cavity. <b>Methods:</b> Hydroalcoholic extracts of <i>G. lucidum</i> and pepsin-soluble collagen peptides from <i>R. pulmo</i> jellyfish were prepared and combined to obtain two hydrogel biocomposites with different component ratios. Chemical and structural characterization was performed using HPLC-DAD, SDS-PAGE, FT-IR, circular dichroism, and spectrophotometric assays. Antioxidant activity was assessed by DPPH radical scavenging and reducing power assays, while antimicrobial activity was evaluated against oral pathogens using diffusion and MIC methods. In vitro biological activity was investigated using MTT viability and scratch migration assays on human OSCC cell lines (SCC-9 and HSC-3). <b>Results:</b> The biocomposites preserved the structural integrity of type I collagen and incorporated polysaccharides and polyphenols from <i>G. lucidum</i>. The combined formulations showed enhanced antioxidant and antimicrobial activities compared with collagen alone. In vitro assays demonstrated dose- and time-dependent reductions in OSCC cell viability and delayed cell migration, with effects comparable to those of <i>G. lucidum</i> extract. <b>Conclusions:</b> The <i>G. lucidum</i>-<i>R. pulmo</i> biocomposite exhibits favorable physicochemical properties and demonstrates antioxidant, antimicrobial, and in vitro antitumor activity. These findings support its potential as a multifunctional biomaterial for further investigation as an adjunct approach in oral cancer-related applications.