Designing foods by modifying their form is becoming a plausible strategy to control how foods behave and are digested in the gastrointestinal (GI) tract. Given the global persistence of the type II diabetes and obesity, there is a great need for dietary interventions that target postprandial glucose levels and rate of lipolysis. A well-established structure-function relationship is found between increased viscosity and rate and extent of macronutrient hydrolysis. Nonetheless, the mechanisms underlying such relationships within specific food commodities as a function of GI viscosity are not yet well identified, especially in light of the confinements in the currently available methods for monitoring GI luminal viscosity. A critical review was compiled to summarize the main characteristics of molecular rotors (MR)s, a class of optical probes that are sensitive to microviscosity, their current applications in biological research and their current and potential applications as sensors of physical properties in food science and engineering. MRs were integrated with TNO Intestinal Model-1 (TIM-1) in a novel method to facilitate detection of in situ changes in luminal viscosity during in vitro GI digestion, respectively. This method was verified using maize starch samples that varied in their amylose-to-amylopectin ratio, and is applicable when microviscosity is representative of bulk viscosity. We were able to correlate food form, and digestion kinetics in several food matrices. Carbohydrate digestion kinetics and in vitro gastric viscosity of three commercially available oat products, instant oats (IO), steel cut oats (SC), and oat bran (OB), were assessed. Findings included: rate of starch digestion in IO > OB > SC; IO and OB viscosities were highest at the onset of digestion and decreased with time, whereas SC onset viscosity was lowest and increased with time. IO- and SC-based meals were modified by addition of a thickening agent, milk protein concentrate (MPC), at concentrations: 0 g, 5 g, and 10 g. Oat-based meals containing 5 g or 10 g MPC yielded significantly less total bioaccessible sugar, a more rapid rate of starch digestion, and higher gastric viscosity compared with those containing 0 g MPC. Physico-chemical properties of human breast milk were compared to four SimilacTM infant formulas, and correlated with in vitro free fatty acid bioaccessibility. Breast milk samples were distinctly unique from the infant formulas: having lower viscosities as a function of pH (pH 6.5 to 3.0), a lag period during lipid digestion, and a higher rate of lipolysis. These findings suggest that modification of food form and formulation alters macronutrient bioaccessibility and luminal viscosity.