A green and efficient 1,3-dipolar cycloaddition of nitrones with different styrenes and cinnamates using a catalytic amount of γ-cyclodextrin (γ-CD) in water has been developed to give substituted isoxazolidines. γ-CD was found to be highly efficacious in carrying out this reaction under an eco-friendly environment, affording moderate to excellent yields and, in some cases, excellent diastereomeric excess (up to >95%) at 100 °C in 8-12 h. The catalyst can be easily recuperated and recycled for several times without loss of activity. Water, an eco-friendly reaction medium, has been utilized for the first time, to the best of our knowledge, in this reaction. The credit of the presented protocol includes high yields and catalyst reusability, and precludes the use of organic solvents. The use of in silico calculations allowed us to rationalize the obtained results and to improve the stereoselectivity.