Marine sponges are a promising source of bioactive secondary metabolites, contributing hundreds of novel compounds per year to natural product research, each with diverse chemical and biological properties. We have chosen to highlight marine natural products that exhibited unique structural features and/or significant bioactivity. The most common report of pharmacological significance was cytotoxicity, with antimicrobial and enzyme inhibition activities following, and mentions of other attributes, such as anti-inflammation, neuroprotection, and anti-biofilm. This review describes newly isolated constituents from sponges between 2020 and 2023 alongside their relevant pharmacological activity. The isolation, structures, and biological properties of 218 unique secondary metabolites from various chemical families, including terpenoids, peptides, and alkaloids from marine sponges, are covered.