The cGAS-STING pathway is a critical component of the innate immune system, playing a pivotal role in immunotherapy. This review discusses the molecular traits and functions of the cGAS-STING pathway and summarizes the development of cGAS-STING agonists and inhibitors. Cyclic dinucleotides (CDNs) are the most common agonists, while inhibitors aim to block the enzymatic activity or DNA binding ability of cGAS. Non-CDN compounds and cGAS agonists are also gaining attention. The overactivation of the cGAS-STING pathway can lead to undesired inflammatory responses and autoimmune diseases, highlighting the need for both agonists and inhibitors. The review covers the mechanisms of action, clinical trials, and challenges in developing these modulators, emphasizing the potential of cGAS-STING pathway targeting in cancer and autoimmune disease treatments. Despite the promising results in preclinical studies, clinical challenges remain, including poor efficacy, limited pharmacokinetics, and potential side effects. Future research should focus on improving the pharmacokinetics, reducing systemic inflammatory responses, and developing tissue-targeting properties to minimize adverse reactions.The cGAS-STING pathway is a critical component of the innate immune system, playing a pivotal role in immunotherapy. This review discusses the molecular traits and functions of the cGAS-STING pathway and summarizes the development of cGAS-STING agonists and inhibitors. Cyclic dinucleotides (CDNs) are the most common agonists, while inhibitors aim to block the enzymatic activity or DNA binding ability of cGAS. Non-CDN compounds and cGAS agonists are also gaining attention. The overactivation of the cGAS-STING pathway can lead to undesired inflammatory responses and autoimmune diseases, highlighting the need for both agonists and inhibitors. The review covers the mechanisms of action, clinical trials, and challenges in developing these modulators, emphasizing the potential of cGAS-STING pathway targeting in cancer and autoimmune disease treatments. Despite the promising results in preclinical studies, clinical challenges remain, including poor efficacy, limited pharmacokinetics, and potential side effects. Future research should focus on improving the pharmacokinetics, reducing systemic inflammatory responses, and developing tissue-targeting properties to minimize adverse reactions.