Abstract The development of altermagnets is fundamentally important for advancing spintronic device technology but remains impractical for the weak spin splitting in most cases, especially in 2D materials. Based on spin group symmetry analysis and first‐principles calculations, a novel hydroxyl rotation strategy in collinear antiferromagnets is proposed to design altermagnets. This approach achieves a large chirality‐reversible spin splitting exceeding 1130 meV in α 60 ‐Mn 2 B 2 (OH) 2 monolayer. The system also exhibits intrinsic features of a node‐line semimetal in the absence of spin‐orbit coupling. Besides, the angles of hydroxyl groups serve as the primary order parameter, which can switch on/off the altermagnetism coupled with the ferroelastic mechanism. The corresponding magnetocrystalline anisotropy have also been modulated. Moreover, an interesting spin‐related transport property with the spin‐polarized conductivity of 10 19 Ω −1 m −1 s −1 also emerges. These findings uncover the hydroxyl rotation strategy as a versatile tool for designing altermagnetic node‐line semimetals and opening new avenues for achieving exotic chemical and physical characteristics associated with large spin splitting.