This paper reports the biopolymerization of e-caprolactone, using lipase Novozyme 435 catalyst at varied impeller speeds and reactor temperatures. A multilayer feedforward neural network (FFNN) model with 11 different training algorithms is developed for the multivariable nonlinear biopolymerization of polycaprolactone (PCL). In previous works, biopolymerization carried out in scaled-up bioreactors is modeled through FFNN. No review discussed the role of different training algorithms in artificial neural network on the estimation of biopolymerization performance. This paper compares mean absolute error, mean square error, and mean absolute percentage error (MAPE) in the PCL biopolymerization process for 11 different training algorithms that belong to six classes, namely (1) additive momentum, (2) self-adaptive learning rate, (3) resilient backpropagation, (4) conjugate gradient backpropagation, (5) quasi-Newton, and (6) Bayesian regulation propagation. This paper aims to identify the most effective training method for biopolymerization. Results show that the quasi-Newton-based and Levenberg–Marquardt algorithms have the best performance with MAPE values of 4.512, 5.31, and 3.21% for the number of average molecular weight, weight average molecular weight, and polydispersity index, respectively.