Wetlands are an important methane (CH4) emission source. CH4 is mainly produced during the biogeochemical process, in which methanogens and methanotrophs both play important roles. However, little is known how these two microbial communities change under different water regimes. In this study, the diversity and abundance of methanogens and methanotrophs in wetlands on Qinghai-Tibetan Plateau with different water contents (a high water content site DZ2-14-3 and a low water content site DZ2-14-4) were studied by using phylogenetic analysis and quantitative PCR based on mcrA gene and pmoA gene. A total of 16 methanogenic operational taxonomic units (OTUs) and 9 methanotrophic OTUs are obtained. For methanogens, Fen cluster (58.0%) and Methanosaetaceae (20.3%) are the dominant groups in high moisture samples, whereas Methanosaetaceae (32.4%), Methanosarcinaceae (29.4%), and Methanobacteriaceae (22.1%) are prevalent in low moisture samples. Methylobacter (90.0%) of type I methanotrophs are overwhelmingly dominant in high moisture samples, while Methylocystis (53.3%) and Methylomonas (42.2%) belonging to types II and I methanotrophs are the predominant groups in low moisture samples. Furthermore, qPCR analysis revealed that the abundance of methanogens and methanotrophs were higher in high moisture samples than that in low moisture samples. Overall, this comparative study between wetlands controlled by two different water regimes on the Qinghai-Tibetan Plateau provides fundamental data for further research on microbial functions within extreme ecosystems.