Acute inflammation may develop into chronic, life-threatening inflammation-related diseases if left untreated or if there are persistent triggering factors. Cancer, diabetes mellitus, stroke, cardiovascular diseases, and neurodegenerative disorders are some of the inflammation-related diseases affecting millions of people worldwide. Despite that, conventional medical therapy such as non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious adverse effects; hence, there is an urgent need for a newer and safer therapeutic alternative from natural sources. Iridoids are naturally occurring heterocyclic monoterpenoids commonly found in Rubiaceae plants. Plant extracts from the Rubiaceae family were demonstrated to have medicinal benefits against neurodegeneration, inflammation, oxidative stress, hyperglycaemia, and cancer. However, the therapeutic effects of natural iridoids derived from Rubiaceae as well as their prospective impacts on inflammation in vitro and in vivo have not been thoroughly explored. The databases of PubMed, Scopus, and Web of Science were searched for pertinent articles in accordance with PRISMA-ScR guidelines. A total of 31 pertinent articles from in vitro and in vivo studies on the anti-inflammatory potentials of iridoids from Rubiaceae were identified. According to current research, genipin, geniposide, and monotropein are the most researched iridoids from Rubiaceae that reduce inflammation. These iridoids primarily act by attenuating inflammatory cytokines and mediators via inhibition of the NF-κB signalling pathway in various disease models. A comprehensive overview of the current research on the anti-inflammatory properties of iridoids from the Rubiaceae family is presented in this review, highlighting the characteristics of the experimental models used as well as the mechanisms of action of these iridoids. To develop an alternative therapeutic agent from iridoids, more studies are needed to elucidate the effects and mechanism of action of iridoids in a wide variety of experimental models as well as in clinical studies pertaining to inflammation-related diseases.