The objective of this study was to evaluate the effect of the addition of BGP-15 ((Z)-N'-(2-hydroxy-3-(piperidin-1-yl) propoxy) nicotinimidamide) on goat sperm during cryopreservation. The semen from six rams was diluted with a soybean lecithin-based extender containing different doses of BGP-15 (0, 50, 100, 150, and 200 μM). After the freeze-thawing process, sperm characteristics, plasma membrane integrity and functionality, acrosomal status, mitochondria activity, apoptosis status, and gene expression of post-thawed ram spermatozoa were assessed. Compared to fresh spermatozoa, the ultrastructure of frozen spermatozoa was damaged, and frozen spermatozoa had a reduced number of duplex microtubules with partially asymmetric distributions, localized disappearance of the central microtubule, and ambiguous submicrotubule structures. Moreover, the 100 μM BGP-15 treatment group had the highest percentage of viability, plasma membrane and acrosome integrities, and mitochondrial activity of frozen-thawed spermatozoa when compared to the control (P <
0.05). In the Computer-Assisted Semen Analyzer, sperm motility parameters were significantly increased in the BGP-15 treatment group against the control group (P <
0.05), except wobble. Similarly, BGP-15 treatment increased the levels of T-AOC, SOD, CAT, and GHS-Px and decreased the level of ROS which compared to controls (P <
0.05). Only the 100 μM BGP-15 treatment group had a higher MDA level than the control group (P <
0.05). In all BGP-15 treatment groups, the mRNA expressions of the ROMO1 gene were significantly reduced compared to controls (P <
0.05), and the mRNA expressions of the SMCP, MnSOD, and CuZnSOD genes were significantly increased (P <
0.05). While the difference in the mRNA expression of the SMOX gene between the 50 μM BGP-15 treatment group and the control group was not significant (P >
0.05). Moreover, the apoptosis rate of freeze-thawed spermatozoa significantly decreased in the 100 μM BGP-15 treatment group compared to the control (P <
0.05), while the MMP of freeze-thawed spermatozoa significantly enhanced in the 100 μM BGP-15 treatment group (P <
0.05). In conclusion, BGP-15 enhances cryo-protective effects on goat spermatozoa, and 100 μM BGP-15 addition to the extender during cryopreservation is beneficial to the goat breeding industry.