Despite being an orphan during the Great Depression, Bud is blessed with a plethora of people showing him huge acts of kindness. Picking which two acts of kindness were "most significant" is up to individual readers, so I'll discuss more than two in order to help give you a starting point for discussion and final judgment.
While I personally don't think the Amos household deserves an award for showing the most significant act of kindness, I would be remiss not to include them. While Todd Amos is the definition of a bully and a jerk, his family was kind enough to try and adopt Bud. They sought out the orphanage and willingly took on the care of another child during a very difficult time in history. Perhaps without Todd in the picture, it might have worked out for Bud.
I believe that the librarian showed Bud multiple acts of kindness by letting him come into the library, peruse books, and even fall asleep in the library. She even helped Bud figure out how far away various cities were.
The next character to show extreme kindness is Lefty Lewis. Lewis decides to stop his car and engage with Bud in Owosso, at night, where either of them could be caught and killed just for being there. Lewis convinces Bud to come home with him where Bud is fed, cleaned up, and given new clothes. Lewis even takes it upon himself to drive Bud into Grand Rapids and take him to where Calloway is.
Finally, Calloway's entire band shows kindness to Bud by taking him in, giving him jobs, and not treating him like some homeless street urchin. Their kindness is not lost on Bud either, and he breaks down weeping at one point because of their kindness and family feel.