The article addresses the topical problem of the loss of biological diversity and approaches its assessment through the case of the fish population of Lake Pskov. The input for the analysis of changes in the structure of the fish component of the lake community was fishery statistics for the period 1960–2023. For mathematical and statistical analysis, the primary dataset on industrial fish catches was divided into five-year periods. Despite the selectivity of fisheries, the structure of catches in the long-term observation series quite adequately reflects the dynamics of the fish population and changes in its species diversity, represented by the composition of catches and the biomass ratios of different fish species. However, the reliability of the assessments of the diversity decline trend by different biodiversity indices is equivocal. Therefore, the aim of this work was to compare how meaningful the different biodiversity indices are in assessing the species diversity dynamics in the fish population of Lake Pskov. The following six indices were used: Shannon index (H), Pielou index (E), Sheldon index (SH), Zhivotovsky index (μ), Simpson’s dominance index (C), Simpson’s diversity index (D). The matrix of paired correlations of the biodiversity indices used to assess changes in the diversity of the species structure of the Lake Pskov fish population is presented. Simpson’s dominance and diversity indices (C and D) proved to be the most meaningful. From 1960 to 2023, the Simpson’s diversity index (D) increased from D = 3.70 to 5.88, showing a “high” positive trend (on the Chaddock scale, correlation coefficient r = 0.85). In addition, application of the Simpson’s diversity index revealed the effect of abiotic factors on the dynamics of the fish population diversity in Lake Pskov. For the period 2000–2023, the following mathematical models were built: Simpson’s diversity index – water level, water temperature, total phosphorus concentration, biochemical oxygen demand for five days, chemical oxygen demand. An adequate relationship was found between the Simpson’s diversity index (D) and total phosphorus concentrations in the lake water, which reflects the negative impact of the eutrophication process on the fish population of Lake Pskov.