A series of N-(alkyl/aryl/heteroaryl)-1-nitro-10H-phenoxazine-3-sulfonamides was designed, synthesized and evaluated for its hypoglycemic, hyperglycemic and oral anti-diabetic activities. These compounds were prepared via the construction of a phenoxazine ring containing nitro and sulfonic acid groups in a single step followed by further transformations. One of these compounds exhibited promising anti-diabetic activities comparable to glibenclamide and increased serum insulin levels indicating its potential as a novel insulin secretagogue.