The rural residential land (RRL) in natural reserves has been deeply transformed due to the disturbance constrained by ecological protection policies. Exploring the distribution characteristics and driving factors of RRL in natural reserves and non-natural reserves will help to promote the governance of land space and alleviate the contradiction of land use. Therefore, taking 122 county-level administrative regions in Hunan Province as an example, this article analyzes and compares the spatiotemporal distribution characteristics of RRL in natural reserves and non-natural reserves by using land use change dynamics, nuclear density analysis, the transfer matrix model, and the ordinary least-squares model and explores how the establishment of natural reserves affects the RRL area change. The results show that (1) the overall RRL area in Hunan changed from 171,162.27 hm2 in 2000 to 169,914.6 hm2 in 2020, with a total reduction of 1,247.67 hm2 and a decrease of 0.73%, and the distribution of the RRL area change presented a hot trend in the northeast and a cold trend in the southwest. (2) The occupation of urban construction land is the main reason for the reduction in RRL area, and the transformation of cultivated land and forestland into RRL is the main source of the increase in RRL area. (3) During 2000–2020, the overall RRL in natural reserves increased by 1,538.37 hm2, with an increase of 0.11%, while the overall RRL in non-natural reserves decreased by 2,786.04 hm2, with a decrease of 0.14%. (4) The establishment of natural reserves has a significant negative correlation with the area of RRL in 2000, 2010, and 2020, indicating that the establishment of natural reserves can limit the growth speed of the RRL area to a certain extent, but is affected by factors such as economic development and rural population growth; it cannot directly promote the overall reduction of RRL area. The results of this study can provide a reference for decision-making related to the spatial structure optimization of natural reserves and non-natural protected RRL and the coordinated development of urban and rural areas.