A better understanding of climate change impact on dry/wet conditions is crucial for agricultural planning and the use of renewable energy, in terms of sustainable development and preservation of natural resources for future generations. The objective of this study was to investigate the impact of climate change on temporal fluctuations of dry/wet conditions in Serbia on multiple temporal scales through multifractal analysis of the standardized precipitation evapotranspiration index (SPEI). We used the well-known method of multifractal detrended fluctuation analysis (MFDFA), which is suitable for the analysis of scaling properties of nonstationary temporal series. The complexity of the underlying stochastic process was evaluated through the parameters of the multifractal spectrum: position of maximum α0 (persistence), spectrum width W (degree of multifractality) and skew parameter r dominance of large/small fluctuations). MFDFA was applied on SPEI time series for the accumulation time scale of 1, 3, 6 and 12 months that were calculated using the high-resolution meteorological gridded dataset E-OBS for the period from 1961 to 2020. The impact of climate change was investigated by comparing two standard climatic periods (1961–1990 and 1991–2020). We found that all the SPEI series show multifractal properties with the dominant contribution of small fluctuations. The short and medium dry/wet conditions described by SPEI-1, SPEI-3, and SPEI-6 are persistent (0.5<α0<1); stronger persistence is found at higher accumulation time scales, while the SPEI-12 time series is antipersistent (0<α0−1<0.5). The degree of multifractality increases from SPEI-1 to SPEI-6 and decreases for SPEI-12. In the second period, the SPEI-1, SPEI-3, and SPEI-6 series become more persistent with weaker multifractality, indicating that short and medium dry/wet conditions (which are related to soil moisture and crop stress) become easier to predict, while SPEI-12 changed toward a more random regime and stronger multifractality in the eastern and central parts of the country, indicating that long-term dry/wet conditions (related to streamflow, reservoir levels, and groundwater levels) become more difficult for modeling and prediction. These results indicate that the complexity of dry/wet conditions, in this case described by the multifractal properties of the SPEI temporal series, is affected by climate change.