Calovius opposed the Catholics, Calvinists and Socinians, and in particular attacked the syncretism of his bitter enemy, George Calixtus. While Calixtus affirmed that the Apostles' Creed was an adequate definition of faith, Calovius rather held that one must believe every part of revealed truth in order to gain salvation. This led Calovius to deny as a heresy the idea that Roman Catholics or Calvinists could be partakers of salvation.
As a writer of polemics Calovius had few equals. His chief dogmatic work, Systema Iocorum theologicorum, (12 volumes, 1655-1677) represents the climax of Lutheran scholasticism. He produced a commentary on Martin Luther's translation of the Bible, the Biblia Illustrata, today known as the Calov Bible. It is written from the point of view of a very strict belief in inspiration, his object being to refute the statements made by Hugo Grotius in his Commentaries.