Digital microfluidic biochips (DMFBs) are increasingly important used for clinical diagnostics drug discovery and point-of-care. Those procedures require high output precision, so the reliability and lifetime of the chips are extremely important. Due to the inherently reconfigurable nature of DMFBs, a degraded electrode may be reused many times. Therefore, the lifetime of the chips is closely related to the total actuation time of an electrode. Thus, the electrode total actuation time needs to be considered carefully in an efficient DMFB design process. This paper proposes an improved whale optimization algorithm (IWOA), which can reduce the excessive use of an electrode and reuse electrodes in an average manner to optimize the longest lifetime of DMFBs. First, the IWOA combined a WOA with a genetic algorithm, and inertial weights were added to enhance the local search ability of the IWOA. Second, the max-min WOA was proposed in the exploration phase. Lastly, the position mass of individual whales was improved to represent the sequence of operations. The simulation experimental results showed that this algorithm was able to solve lifetime optimization problems. The efficiency and convergence performance of the algorithm were very good. The proposed algorithm can achieve maximum improvement in the maximum electrode activation time of 74.6%, 8.2%,15.7% and 7.2% respectively, compared with T-trees algorithm, 3-DDD algorithm, PRSA algorithm and 3D-DDMS algorithm.