Starch digestion rate and location in the gastrointestinal tract (GIT) are critical for human health. This review aims to present a comprehensive summary on our current understanding of physiological, biochemical, anatomical and geometrical factors of human digestive system that are related to in vivo starch digestibility. It is shown that all digestive compartments including mouth, stomach, small intestine, and large intestine play critical roles in regulating the overall starch digestion process. A proper investigation of starch digestion pattern should thus be based on the consideration of all these compartments. Main biological factors are summarized as oral mastication and salivation, gastric emptying and motility, small intestinal enzymes and motility, large intestinal resistant starch (RS)-microbiota interactions and gut-brain feedback control, as well as glucose adsorption and hormonal feedback control. However, connections among these biological factors in determining starch digestive behaviors remain elusive. This is due to the inherent complexity of human GIT anatomy, motility and biochemical conditions, as well as ethical, financial and technical issues in conducting clinical studies. Much technological and scientific efforts from both clinical studies and in vitro simulation models are required for a better understanding of in vivo starch digestion behaviors.