The cGAS-STING pathway is crucial in immunotherapy, with agonists and inhibitors being developed for various diseases. Agonists activate STING, primarily through cyclic dinucleotides (CDNs), while inhibitors block cGAS activity or DNA binding. Non-CDN compounds and cGAS agonists are also gaining attention. The pathway's overactivation can lead to inflammation and autoimmune diseases, necessitating both agonists and inhibitors. This review summarizes the molecular traits and roles of the cGAS-STING pathway, along with the development of agonists and inhibitors. The information is intended to aid in designing novel drugs targeting the pathway. Agonists include CDNs like cGAMP, which activate STING and induce IFN-I production, enhancing antitumor immune responses. Non-CDN agonists such as DMXAA, SR-717, and MSA-2 also show promise. Metal-based agonists, like platinum drugs and manganese complexes, can damage DNA and activate the pathway. Other agonists include β-arrestin 2 and chitosan, which enhance cGAS activity. Inhibitors target STING palmitoylation, CDN pocket, or TBK1. Examples include nitrofuran derivatives and specific STING inhibitors. cGAS inhibitors block ATP/GTP binding or dsDNA interaction. These inhibitors include compounds like 33, 34, and 35, which selectively inhibit cGAS activity. Despite progress, challenges remain, including poor efficacy in clinical trials, pharmacokinetic issues, and systemic toxicity. Future research should focus on improving pharmacokinetics, reducing side effects, and enhancing tumor selectivity. The cGAS-STING pathway holds promise for cancer and autoimmune disease treatment, but careful modulation is needed to avoid adverse effects.The cGAS-STING pathway is crucial in immunotherapy, with agonists and inhibitors being developed for various diseases. Agonists activate STING, primarily through cyclic dinucleotides (CDNs), while inhibitors block cGAS activity or DNA binding. Non-CDN compounds and cGAS agonists are also gaining attention. The pathway's overactivation can lead to inflammation and autoimmune diseases, necessitating both agonists and inhibitors. This review summarizes the molecular traits and roles of the cGAS-STING pathway, along with the development of agonists and inhibitors. The information is intended to aid in designing novel drugs targeting the pathway. Agonists include CDNs like cGAMP, which activate STING and induce IFN-I production, enhancing antitumor immune responses. Non-CDN agonists such as DMXAA, SR-717, and MSA-2 also show promise. Metal-based agonists, like platinum drugs and manganese complexes, can damage DNA and activate the pathway. Other agonists include β-arrestin 2 and chitosan, which enhance cGAS activity. Inhibitors target STING palmitoylation, CDN pocket, or TBK1. Examples include nitrofuran derivatives and specific STING inhibitors. cGAS inhibitors block ATP/GTP binding or dsDNA interaction. These inhibitors include compounds like 33, 34, and 35, which selectively inhibit cGAS activity. Despite progress, challenges remain, including poor efficacy in clinical trials, pharmacokinetic issues, and systemic toxicity. Future research should focus on improving pharmacokinetics, reducing side effects, and enhancing tumor selectivity. The cGAS-STING pathway holds promise for cancer and autoimmune disease treatment, but careful modulation is needed to avoid adverse effects.