What Shemirah is discussed?
Rashi: We want to guard ourselves from questioning [the fairness of] Midas ha'Din, even though afflictions come upon us and Resha'im pain us.
Radak: (a) I will guard my way, i.e. my conduct and affairs. This is like "me'Asos Derachecha" (Yeshayah 58:13). (b) I will guard my mouth from saying what is not so, like it says "b'Chol Zos Lo Chata Iyov bi'Sefasav" (2:10).
Malbim: Initially I thought not to speak about this investigation of the Nefesh, for two reasons. (a) The essence of the Nefesh is hidden from man's intellect. Man perceives only via senses. One cannot recognize the Nefesh via senses! Perhaps I will sin, and think that the Nefesh is from the same physical substance as the body, and perishes like the body does; this is denial of the eternity of the Nefesh. (b) Even if I trust with strong Emunah that I will not come to say so, I should muzzle my words while the Rasha is opposite me, lest my words be a stumbling block.
What is "Machsom"?
Rashi: It is like "Lo Sachsom Shor" (Devarim 25:4, i.e. a muzzle).
Why does it say "b'Od Rasha l'Negdi"?
Radak: All the more so while the Rasha is opposite me - he comes to visit me and see my pain and demise - I will guard my mouth. Even the scream that a Choleh usually lets out amidst his pain, I will refrain from it in front of the Rasha, lest he rejoice over me.
Erech Apayim (1, note 22, citing Chut ha'Meshulash): David was humble and patient with Resha'im "l'Negdi", but he was harsh and brazen against Resha'im Neged Hashem.