Fungi have been an extraordinary area of scientific research, and many secondary metabolites with intriguing chemical diversity along with interesting biological activities have been identified. Fungi like Phoma sp. have been investigated as a source of structurally unique metabolites over the past 10 years (2011–2020). A diverse range of natural products, viz., α-pyrone derivatives, isocoumarins, anthraquinones, xanthones, thiodiketopiperazines, cytochalasin derivatives, diphenyl ether derivatives, furopyrans, xyloketals, chromones, meroterpenoids, diterpenoids, polyketides, and alkaloids, have been reported from various Phoma spp. These metabolites illustrated phytotoxic, cytotoxic, antibacterial, antifungal, herbicidal, immunosuppressive, antiviral, antidiabetic (PTP1B inhibition), anti-Alzheimer (acetylcholinesterase inhibition), and antioxidant activities. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.