Multi-laminated drug controlled release devices are one of the most commonly used drug controlled release devices at present. In order to release the drug into human body according to the predetermined release rate, an optimization approach to achieve desired drug release behavior using multi-laminated drug controlled release devices was proposed. First, based on the idea of inverse problem, the optimization of drug release based on the multi-laminated drug controlled release devices was transformed into an initial value inverse problem of diffusion equations. Then, a modified Tikhonov regularization method was proposed by constructing a new regularizing filter based on the singular value theory of compact operators, and the convergence and the optimal asymptotic order of the regularized solution were obtained. Finally, the modified Tikhonov regularization method was applied to the optimization of the initial drug concentration distribution. For three targeted release requirements (constant release, linear decrease release, and linear increase followed by a constant release), better results could be achieved by using the optimized initial drug concentration distributions obtained by the modified Tikhonov regularization method. Numerical results demonstrate that the modified Tikhonov regularization method not only had the optimal asymptotic order, but also had a good effect on optimizing the multi-laminated controlled release device. By using the modified Tikhonov regularization method to optimize the initial concentration of the drug in the multi-laminated controlled release device, the drug release behavior of the system was basically realized as constant velocity release behavior, quasi-linear release behavior, and non-linear release behavior.