John Chrysostom

For He said not, Go and say unto her, She is not My mother, but continues His discourse to him that had brought Him word; as it follows; But he answered and said unto him that told him, Who is my mother? and who are my brethren? But had He desired to disown His mother, He would have done it at the time when the Jews cast His birth in His teeth.

Catena Aurea by Aquinas ↗

Theophylact of Ohrid

He did not say this to offend His mother, but to correct this vainglorious and human thought of hers. For He did not say, "She is not My mother," but "Unless she does the will of God, that she bore Me is of no benefit to her." He does not deny the relationship by birth, but He adds to it the relationship by virtue. For no unworthy person derives benefit from a relationship by birth. When He had corrected the sickness of vainglory, He once again obeyed His mother who was calling Him. For the evangelist says:

Commentary on Matthew ↗

Gregory the Dialogist

For Jesus, our Creator and Redeemer, pretends not to know His mother, and indicates who is His mother and who are His relatives not through kinship of the flesh, but through union of the spirit, saying: "Who is my mother, and who are my brethren? …

Forty Gospel Homilies, Homily 3 ↗

Hilary of Poitiers

And He cannot be held to have thought meanly of His mother, seeing that in His passion He evinced the most extreme carefulness for her.

Catena Aurea by Aquinas ↗

Thomas Aquinas

But he replied... Here he gives Christ's reply and does two things: first, he replies; secondly, he commends his disciples (v. 49). He says, "Who is my mother and who are my brothers?" From these words some have denied that Christ truly assumed flesh, but only seemed to. Hence they explained: this is not my mother and these are not my brothers. …

Commentary on Matthew ↗