RNA molecules play a significant role in cell function especially including pseudoknots. In past decades, several methods have been developed to predict RNA secondary structure with pseudoknots and the most popular one uses minimum free energy. It is a nondeterministic polynomial-time hard (NP-hard) problem. We have proposed an approach based on a metaheuristic algorithm named Chemical Reaction Optimization (CRO) to solve the RNA pseudoknotted structure prediction problem. The reaction operators of CRO algorithm have been redesigned and used on the generated population to find the structure with the minimum free energy. Besides, we have developed an additional operator called Repair operator which has a great influence on our algorithm in increasing accuracy. It helps to increase the true positive base pairs while decreasing the false positive and false negative base pairs. Four energy models have been applied to calculate the energy. To evaluate the performance, we have used four datasets containing RNA pseudoknotted sequences taken from the RNA STRAND and Pseudobase++ database. We have compared the proposed approach with some existing algorithms and shown that our CRO based model is a better prediction method in terms of accuracy and speed.