As one of the key hydrolytic enzymes for starch digestion, the hydrolysis of α-amylase enables rapid starch digestion, leading to a rapid rise in postprandial blood glucose levels. Persistent postprandial blood glucose increases are positively correlated with metabolic diseases such as diabetes, hyperglycemia and hyperlipidemia. Using natural compounds to inhibit the activity of α-amylase is of great significance in reducing the incidence of these metabolic diseases. Using chlorogenic acid and α-amylase as the research object, the in vitro simulated digestion experiment was carried out. When the substrate concentration was 10 mg/mL, the activity of α-amylase was 2 U/mL. when the hydrolysis time was 20 min, the inhibition rate was 67.3%, and the IC50 was 4.2 mg/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 method found 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 α-amylase substrate complex. Based on the inhibitory effect of chlorogenic acid on α-amylase, it might illuminate an approach towards the strategic inhibition of digestive enzymes by chlorogenic acid and provide some new insights into the utilization of chlorogenic acid for slowing starch digestion. It might provide theoretical basis and beneficial reference for the designing foods for type II diabetic patients with chlorogenic acid.