Casein micelle as a biodegradable polymer has been used to encapsulate sambiloto (Andrographis paniculata) containing andrographolide compound as anti-diabetic herbal drug based on natural ingredients. Major obstacle of oral drug release system is gastrointestinal tracts in the body. Therefore, it is necessary to study release of sambiloto herbal drug to determine its accuracy which is expected can be sustained in the small intestine. In vitro release of this herbal drug had been studied by analyzing casein degradation in simulated gastric and intestinal fluid in presence of protease enzyme i.e, pepsin and pancreatin. In 2 hour simulated gastric fluid digestion (ratio substrate: enzyme optimum (w/w) 5:1), casein degradation tends to give a burst release profile in less than 30 minutes digestion. The presence of sambiloto in casein micelles slows casein degradation in simulated gastric fluid digestion. In 6 hours, the simulated intestinal fluid digestion (ratio substrate: enzyme optimum (w/w) 500:1), casein degradation tends to give a sustained release profile in about 4 hours digestion. Casein degradation profile tends to give burst release in first 30 minutes digestion in simulated intestinal fluid digestion when herbal drug was digested in simulated gastric - intestinal fluid.