Barium sulphate (BS), usually administered as an oral suspension, is a widely prescribed GI contrast agent. Consumption of BS is reported with side effects like mild stomach cramps, nausea, vomiting, diarrhoea, etc. This can be attributed to its high dosage, which is 9 g and 18 g in infants and adults, respectively. Considering its physicochemical properties, one approach to minimize BS dose is formulating its nanosuspension dose due to the higher surface area to volume ratio of nanoparticles. We formulated BS nanosuspension with the help of an industrially scalable and green Microfluidizer technology. Nanonization of coarse suspension was performed using Microfluidizer technology. The microfluidization process was optimized for parameters like the number of cycles and pressure to achieve the desired stable sub-micron particle size. A quantitative gravimetric assay was performed as per the protocol mentioned in the Indian Pharmacopeia. Ex vivo mucoadhesion studies were performed on intestinal tissue samples from goat. Comparative contrasting efficacy of the developed nanosuspension with the marketed formulation was evaluated in vivo in rabbits. The average particle size of coarse BS suspension was 20 μm. After subjecting to optimized microfluidization, the particle size of 700 nm was achieved. The formulation was found to be stable for 6 months as per ICH guidelines. BS nanosuspension showed better contrasting as compared to the marketed formulation in in vivo studies. A greener, industrially scalable microfluidization technology was successfully used for the fabrication of BS nanosuspension that has translational potential, with a prospective reduction in side effects of the current formulation.