This paper takes Dongzhaigang National Nature Reserve and 1 km peripheral zone as the study area, selects Sentinel-2 remote sensing image data from 2017—2021, decodes landscape types using human-computer interaction, calculates landscape pattern index, and then compares and analyzes the landscape pattern changes inside and outside the reserve during the 5-year period and its main driving forces. The results show that (1) within the protected area, the mangrove wetland area shows an increasing trend, the woodland area decreases, and the cultured water area decreases significantly; the protected area has better landscape connectivity and lower fragmentation, among which mangrove is the dominant landscape. (2) In the peripheral zone, the area of mangrove wetlands has increased, the area of woodland has decreased, the area of cultured water surface and construction area have decreased, but the area of cultivated land has increased; compared with the protected area, the landscape fragmentation is higher and the connectivity and integrity are poor. (3) Mangrove ecological conservation and restoration activities were the main drivers of significant changes in the landscape pattern of the protected area, while human activities such as farming and construction were the main factors that changed the landscape pattern of the peripheral zone. The results of the study are of reference value for optimizing the conservation management of the reserve and strengthening the control of human activities in the peripheral zone.