<p>Marine-derived <i>Penicillium</i> fungus gained significant attention in recent years due to their potential as a valuable source of unique natural compounds with a wide range of chemical structures and bioactive capabilities. The primary origins of marine-derived <i>Penicillium</i> fungi are mangroves, sediments, marine shrimps, corals, starfish, algae, and sponges. A total of 390 unique natural compounds were extracted from <i>Penicillium</i> fungi which were found in marine environments. These compounds primarily consist of polyketides, alkaloids, terpenoids, chromone derivatives, anthraquinones, citrinins, steroids, azaphilones, and macrolides. Biological studies demonstrated that these compounds exhibit antimicrobial, anti-inflammatory, cytotoxic, pesticide development, neuroprotective, anti-glioma, anti-proliferative, α-glucosidase inhibitory activities, anti-allergic, photo-protective, anti-angiogenic effect, larvicidal activity, antiviral, anti-diabetic activity, and other activities that could be useful in the development of new drugs. This study shed the light on the recent discovery of bioactive MNPs (marine-derived <i>Penicillium</i>; natural products) derived&#xa0;from <i>Penicillium</i> fungi found in marine environments in the last five years from 2020 to 2025, classified the MNPs based on the sources of the fungi and their specific biological activities. Besides, the results of molecular docking studies recently performed on <i>Penicillium</i> metabolites referring to various biological activities were also compiled in this review. Thus, this review highlighted that <i>Penicillium</i> species obtained from marine organisms act as an everlasting mine of bioactive novel metabolites combating various ailments.</p> Graphical Abstract <p></p>