Alkabetz studied Torah under Rabbi Yosef Taitatzak. In 1529, he married the daughter of Yitzhak Cohen, a wealthy householder living in Salonica. Alkabetz gave his father-in-law a copy of his newly completed work Manot ha-Levi. He settled in Adrianople where he wrote Beit Hashem, Avotot Ahava, Ayelet Ahavim and Brit HaLevi. This latter work he dedicated to his admirers in Adrianople. His students included Rabbi Shmuel Ozida, author of Midrash Shmuel on Avot, and Rabbi Avraham Galante, author of Yareach Yakar on Zohar. His circle included Moshe Alsheich and Yosef Karo, as well as his famous brother-in-law Moshe Cordovero.
Following the practice described in the Zohar of reciting biblical passages known as the Tikūn on the night of Shavuot, Rabbi Shlomo and Rabbi Joseph Karo stayed awake all that night reading. During the recitation of the required texts, Rabbi Karo had a mystical experience: The Shekhinah appeared as a maggid, praising the circle and telling them to move to the Land of Israel. When they stayed up again the second night of Shavuot, the Shekhinah was adamant about their moving to the land of Israel. The account was recorded by Alkabetz. He settled in Safed in 1535.
His works written in Adrianople center on the holiness of the people Israel, the Land of Israel, and the specialness of the mitzvot. Alkabetz accepts the tradition that Esther was married to Mordechai before being taken to the king's palace and becoming queen, and even continued her relationship with Mordechai after taking up her royal post. The view of midrash articulated by Alkabetz and other members of the school of Joseph Taitatsak represents an extension of the view of the authority of the oral law and halachic midrash to aggadic midrash and thus leads to the sanctification and near canonization of aggadic expansions of biblical narrative 
Among his printed works:
Among those existing in manuscript are: