With the increasing proportion of renewable energy generation, the impact of grid three-phase imbalance is becoming more and more apparent, especially the excess negative sequence is an important reason for reducing the safety of power systems. The unified power flow controller (UPFC) has the ability to adjust the output of each sequence current, which can be used to improve the balance of the system. Firstly, an optimal compensation algorithm of UPFC for positive-sequence power flow based on the decoupling-compensation principle is established. Secondly, a current control model of UPFC for negative-sequence compensation is constructed, and the optimization problem of voltage imbalance compensation is attributed to the convex quadratically constrained quadratic programming (QCQP). The primal-dual interior point method is used to obtain the optimal output value of the UPFC negative-sequence current. Finally, an optimal power flow calculation method for negative-sequence voltage compensation considering positive-sequence grid loss and negative-sequence voltage index, as well as an overall compensation strategy for regional negative-sequence voltage, are proposed. The feasibility and effectiveness of the proposed method are verified through example analysis.