The aim of the study was to evaluate the effect of two lossy image compression methods on fractal dimension (FD) calculation. Ten periapical images of the posterior teeth with no restorations or previous root canal therapy were obtained using storage phosphor plates and were saved in TIF format. Then, all images were compressed with lossy JPEG and JPEG2000 compression methods at five compression levels, i.e., 90, 70, 50, 30, and 10. Compressed file sizes from all images and compression ratios were calculated. On each image, two regions of interest (ROIs) containing healthy trabecular bone in the posterior periapical area were selected. The FD of each ROI on the original and compressed images was calculated using differential box counting method. Both image compression and analysis were performed by a public domain software. Altogether, the FD of 220 ROIs was calculated. FDs were compared using ANOVA and Dunnett tests. The FD decreased gradually with compression level. A statistically significant decrease of the FD values was found for JPEG 10, JPEG2000 10, and JPEG2000 30 compression levels (p < 0.05). At comparable file sizes, the JPEG induced a smaller FD difference. In conclusion, lossy compressed images with appropriate compression level may be used for FD calculation.