Obesity, a pervasive global public health challenge, impacts human well-being, and there is a growing interest in the potential of herbs for their anti-obesity effects. However, the specific herbs that possess these properties are not well understood. This study aims to identify and characterize herbs that promote weight loss and to elucidate the mechanisms involved. We employed a high-fat diet (HFD)-induced obesity mouse model to assess the efficacy of various herbs in weight reduction and to explore how these herbs interact with the gut microbiota. By leveraging the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we identified active ingredients present in the herbs and analyzed their regulatory effects on the gut microbiota. Among the 65 herbs, inulin, mori follum, corn silk, maydis seigma, crataegus, taraxacum, portulacae herba, rhizoma gastrodiae, rose rugosae flos, thalluslaminariae were found to significantly reduce body weight and restore the gut microbiota dysbiosis associated with HFD-induced obesity. We found that Blautia, which was enriched by the anti-obesity herbs, was inversely related to triglyceride (TG) levels. Conversely, Desulfovibrio, reduced by the anti-obesity herbs, was a positively linked to weight and weight gain. Furthermore, we discovered that arachidonic acid, shared by three anti-obesity herbs, was associated with beneficial bacteria such as Blautia. Our study identified 10 herbs with anti-obesity properties, detailing their active constituents and their influence on the gut microbiota. Our finding not only identified nearly 10 herbs that significantly reduce body weight, but also contribute to improving the understanding of the regulatory network between herbs and the gut microbiota.