Penicillium species generate a wide range of secondary metabolites that hold significant importance in food and industrial applications. The recent discovery of P. sclerotiorum capability to produce a diverse range of secondary metabolites further emphasizes its ecological and industrial significance. Azaphilone derivatives, a notable class of compounds synthesized by this fungus, have exhibited a wide spectrum of biological activities, including antimicrobial, antiviral, anti-inflammatory, antioxidant, cytotoxic, hypoglycemic, and nematocidal effects. Among these, sclerotiorin stands out for its recognized antioxidant properties, holding immense promise for applications in pharmaceuticals and the food industry due to its potential health benefits. Further exploration into the environmental factors influencing the production of these metabolites could pave the way for optimizing cultivation conditions. This optimization could lead to enhanced yields of these valuable compounds, thereby facilitating their diverse applications across various industrial sectors.