Isinglass, derived from swim bladders of Caspian Sea fish and consisting predominantly of protein collagen, was found to be an effective, easily accessible heterogeneous biocatalyst for the synthesis of biologically important functionalized spirooxindoles and spiroacenaphthylenes in water. This facile and efficient one-pot, three-component synthesis route involving isatin or acenaphthenequinone, activated methylene reagent, and 1,3-dicarbonyl compounds provides a new strategy giving rise to spiro derivatives in quantitative yields in very short reaction times. Graphical abstract N CN X O O R 2 R 1 N O X H2N R 2 R 1 O O O O H2O, 60 °C H2O, 60 °C O O O O X H2N O 6 2 3 4 5 1 X= CN, CO2Et R 1 = H, Me, Et, Bn, Ph R 2 = H, Cl, Br, NO2 IG IG