Introduction: Ramalina conduplicans and Roccella montagnei represent ecologically resilient symbiotic systems that synthesize diverse secondary metabolites with potent antimicrobial potential. Aim/Objective: The present study aimed to evaluate the antifungal and antibacterial activities of solvent extracts from Roccella montagnei and Ramalina conduplicans, traditionally known for their therapeutic properties, against clinically relevant pathogens . Methods: Lichen thalli collected from the Western Ghats of Tamil Nadu were sequentially extracted using diethyl ether, acetone and methanol via Soxhlet hot percolation. Antifungal activity was assessed against Aspergillus niger, Aspergillus flavus, Fusarium oxysporum and Fusarium solani using disk diffusion and broth macrodilution methods. Antibacterial activity was determined by agar well diffusion and broth microdilution assays. Total phenolic and flavonoid contents were quantified spectrophotometrically as gallic acid and quercetin equivalents, respectively. Statistical significance was evaluated using two-way ANOVA (p < 0.05). Results: Ramalina conduplicans and Roccella montagnei exhibited notable antifungal and antibacterial efficacy in a solvent dependent manner. The acetone extract of Ramalina conduplicans produced the largest inhibition zones (10–12 mm) and the lowest MIC values (2–8 μg/mL), particularly against Aspergillus flavus and Fusarium solani. The methanolic extract of Roccella montagnei showed strong antifungal activity (MIC 2–4 μg/mL) with high phenolic (37.28 mg GAE/g) and flavonoid (48.24 mg QE/g) contents. Acetone extracts of both lichens displayed broad-spectrum antibacterial activity, most pronounced against Escherichia coli (21–24 mm ZOI; MIC 4–8 μg/mL). Conclusion: This study highlights R. montagnei and R. conduplicans as promising sources of phenolic rich metabolites with potent antifungal and antibacterial properties. The acetone and methanol extracts demonstrated broad spectrum inhibitory effects, underscoring their potential for developing novel natural antimicrobial agents.