Harmonic pollution sources in microgrids have the characteristics of high penetration and decentralization, as well as forming a full network. Local harmonic mitigation is a traditional harmonic mitigation method, which has the disadvantages of complexity and costly operation. Based on the idea of the decentralized autonomy of power quality, this paper establishes a comprehensive optimization model of the active power and harmonic mitigation capacities of grid-connected inverters based on two-layer optimization and realizes harmonic mitigation. Firstly, based on the harmonic sensitivity analysis, the calculation method of harmonic mitigation capacity is given. Secondly, a two-layer model of harmonic mitigation optimization is established. The upper-layer optimization model takes the minimum operation cost of the microgrid as the objective and the active power reduction in the multi-functional grid-connected inverter (MFGCI) as the optimization variable. The lower-layer optimization model offers the best harmonic mitigation effect as the objective and the harmonic current compensation as the optimization variable. According to the relationship between the total remaining capacity of MFGCI and the capacity required for harmonic mitigation, there are three different objective functions in the lower-layer optimization model. Then, the model solving steps are provided. Finally, an example shows that the proposed optimization model can achieve harmonic mitigation at different times. Compared with the case without active power optimization, the operation cost of the whole system can be reduced by up to 14.6%, while ensuring the harmonic mitigation effect. The proposed method has the advantages of a harmonic mitigation effect and economical system operation.