As one of the key hydrolytic enzymes for starch digestion, the hydrolysis of α-amylase enables starch to digest quickly, leading to a rapid increase of postprandial blood glucose levels. Persistent postprandial blood glucose increase is positively correlated with occurrence of metabolic diseases such as diabetes, hyperglycemia and hyperlipidemia, and etc.. Using natural compounds to inhibit the activity of α-amylase is of great significance in reducing the incidence of these metabolic diseases. Chlorogenic acid and α-amylase taken as the research object, the in vitro simulated digestion experiment was carried out. When the substrate concentration was 10mg/mL, the activity of α-amylase was 2U/mL. When the hydrolysis time was 20min, the inhibition rate was 67.3%, and the IC₅₀ was 4.2mg/mL, which confirmed that chlorogenic acid inhibited the activity of α-amylase. Based on enzyme reaction kinetics, the results of Lineweaver-Burk double reciprocal mapping analysis showed that the inhibition type of the enzyme was mixed inhibition. Molecular docking technique was used to reveal the intermolecular interaction between chlorogenic acid and α-amylase. It was predicted that the inhibition mechanism of chlorogenic acid on α-amylase was a mixed inhibition, which was consistent with the results of enzyme reaction kinetics. Molecular docking simulation results showed that chlorogenic acid could not only form hydrogen bonds with Glu261, Asp328 and Tyr193 at the catalytic active site of α-amylase to achieve competitive inhibition with starch, but also form hydrogen bonds with His327 and Ala232 amino acid residues of α-amylase to achieve non-competitive inhibition combined with amylase-substrate complex. Based on the inhibitory effect of chlorogenic acid on α-amylase, chlorogenic acid could be used to inhibit the activity of α-amylase to reduce the digestibility of starch and delay the rapid increase of postprandial blood glucose caused by carbohydrates. It was hoped to provide a theoretical basis and useful reference for the application of chlorogenic acid in food suitable for type Ⅱ diabetes patients.