Insulin resistance (IR) is a main etiology of various metabolic diseases such as type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia and coronary heart disease. IR is a multi-factorial etiology disease regulated by various mechanisms. Obesity, a significant public health problem worldwide, is considered as a high-risk factor to induce IR and T2DM. Thus, inhibiting obesity-induced IR is one of the key therapeutic strategies to improve T2DM. Natural products from herbs and nutraceuticals have shown promising efficacy on obesity-induced IR and T2DM owing to its multi-component and multi-target characteristics. However, the active constituents and the action mechanisms are still not yet well elucidated. In this review, the natural constituents with protective capacities against IR were summarized. The active constituents include crude extracts such as polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids, as well as monomeric compounds such as curcumin, berberine, capsaicin, naringenin, quercetin, betaine and isoliquiritigenin. The action mechanisms of these active constituents could be mainly divided into 4 categories: ameliorating metabolic abnormality, inhibiting inflammation, reversing gut microbiota dysbiosis, regulating micro RNAs (miRNAs). Their precise roles in regulating PI3K/AKT, AMPK, PPARs, SIRT1 and NF-κB pathways, brown adipose tissue activity and white adipose tissue browning, NLRP3 inflammasome activity, gut microbiota structure and composition and miRNA expression were discussed. The sources, chemical structures, experimental models, pharmacological effects and action targets of these active constituents were also summarized. This review provides new active constituents, therapeutic targets and reasoning for the clinical application of herbs and nutraceuticals in the treatment of IR and T2DM.