The unmanned aerial vehicle (UAV) path planning problem is a type of complex multi-constraint optimization problem that requires a reasonable mathematical model and an efficient path planning algorithm. In this paper, the fitness function including fuel consumption cost, altitude cost, and threat cost is established. There are also four set constraints including maximum flight distance, minimum flight altitude, maximum turn angle, and maximum climb angle. The constrained optimization problem is transformed into an unconstrained optimization problem by using the penalty function introduced. To solve the model, a multiple population hybrid equilibrium optimizer (MHEO) is proposed. Firstly, the population is divided into three subpopulations based on fitness and different strategies are executed separately. Secondly, a Gaussian distribution estimation strategy is introduced to enhance the performance of MHEO by using the dominant information of the populations to guide the population evolution. The equilibrium pool is adjusted to enhance population diversity. Furthermore, the Lévy flight strategy and the inferior solution shift strategy are used to help the algorithm get rid of stagnation. The CEC2017 test suite was used to evaluate the performance of MHEO, and the results show that MHEO has a faster convergence speed and better convergence accuracy compared to the comparison algorithms. The path planning simulation experiments show that MHEO can steadily and efficiently plan flight paths that satisfy the constraints, proving the superiority of the MHEO algorithm while verifying the feasibility of the path planning model.