The club was founded on 7 July 2021 and started competing in the second tier of Macedonian handball. The Alkaloid company owns 100% of the club. RK Alkaloid managed to win the league title in their first season, securing a place in the
Macedonian Handball Super League for 2022–23. They finished 2nd in the 2022-23
Macedonian Handball Super League season and they competed in the
EHF European League group stage for the first time in the season 2023-24. In 2024 Alkaloid won the domestic cup for the first time, followed by the Supercup of Macedonia title. After beating
AEK H.C., Alkaloid became the third Macedonian handball club with a European trophy and the first one to win the
EHF European Cup.
Kiril Lazarov became the first Macedonian to win a European trophy both as a player and a coach. ==Home ground==