Natural products have been a rich source of compounds with structural and chemical diversity for drug discovery. However, antibiotic resistance in bacteria has been reported for nearly every antibiotic once it is used in clinical practice. In the past decade, pharmaceutical companies have reduced their natural product discovery projects because of challenges, such as high costs, low return rates, and high rediscovery rates. The largely unexplored marine environment harbours substantial diversity and is a large resource to discover novel compounds with novel modes of action, which is essential for the treatment of drug-resistant bacterial infections. In this Review, we report compounds derived from marine sources that have shown in-vivo and in-vitro efficacy against drug-resistant bacteria. Analysis of the physicochemical properties of these marine natural products with activity against drug-resistant bacteria showed that 60% of the compounds have oral bioavailability potential. Their overall distribution pattern of drug characteristics agrees with the observation that marketed antibacterial drugs have a polar distribution, with a lower median calculated logP. The aim of this Review is to summarise the diversity of these marine natural products, with a special focus on analysis of drug bioavailability. Such biologically active compounds, with high degrees of bioavailability, have the potential to be developed as effective drugs against infectious diseases.