This study intends to verify how the alteration of the landscape configuration, represented by different metrics of configuration and diversity, is related to the intensity of human disturbance. The objectives of the study are: (1) to quantify the change in land use/land cover (LULC) patterns and the degree of human disturbance in Serbia between 2000 and 2018, and (2) to study the relationship between LULC configuration and the impact resulting from human disturbance under different levels of intensity, to understand how changing trends in landscape pattern can serve as indicators to estimate landscape changes resulting from human actions. The Hemeroby Index (HI) was calculated to quantify the impacts on ecosystems resulting from disturbance caused by human actions. Based on the analysis of the variation in the value corresponding to the HI for the period between 2000 and 2018, the level of naturalness increased by only 5% of the territory of Serbia, with this change being verified mainly in SE Serbia. The landscape pattern was quantified using a set of LULC metrics. We used the Spearman method to identify the existing statistical correlations between the geometric parameters of the landscape and the HIs values. At the landscape level, the Mean Shape Index, Edge Density, Mean Patch Fractal Dimension, and Shannon Diversity Index show a strong negative correlation with HI. This correlation suggests that landscapes with greater structural complexity are good indicators of low levels of hemeroby. At the class level, Edge Density and Mean Patch Size correlate significantly with the HI for artificial surfaces, agricultural areas, forests, and semi-natural areas.