Inflammation is a crucial target for therapeutic interventions in many life-threatening diseases, which sustains ongoing interest in the field of inflammation biology. Plant-derived natural products, rich in phytochemicals, have been used as healing agents in several diseases since antiquity. These compounds exhibit antioxidant, anti-inflammatory, and immunomodulatory properties, as well as gut microbiota modulation. They hold substantial potential as promising candidates for the development of novel strategies in the management of inflammation-associated diseases. This study presents a comprehensive overview of the potential benefits given from administrating natural products (e.g., phenols, terpenes, flavonoids, and saccharides), with a particular emphasis on vitamin C-rich fruits based on the high content of bioactive compounds with anti-inflammatory properties. Apart from natural products, the gut microbiota acts a significant role in modulating the activation of inflammatory reaction. Deviations in its composition have been associated with various diseases. Furthermore, advancements in machine learning contribute to enhancing clinical outcomes in disease treatment. Therefore, this work provided some valuable insights in elaborating the therapeutic potential of vitamin C-rich fruits, the role of probiotics as anti-inflammatory agents, and the utilization of computer-aided drug design techniques.