Samantha Markle -- who has no relationship with Harry or Meghan and has never been with them since they hooked up -- says Meghan and Prince Harry are inevitably heading for a split unless they get some serious counseling and go on an apology tour to undo all the damage they've done to the Royal Family.

It doesn't sound like Sam's holding her breath for that though, and she suggests Harry's probably already questioning his marriage to Meghan ... whom she accuses of nonstop lying.

It's pretty incendiary stuff from Samantha, who thinks it's only a matter of time before Harry pulls away ... and divorce lawyers get involved. Again, she has no connection to the Royals either, but that hasn't stopped her from weighing in.

As we reported ... Meghan's half-sister trashed Meghan earlier this week for turning her back on their family ... claiming she suffers from "narcissistic personality disorder."

During the Oprah interview, Meghan said she's had little to no relationship with Samantha for more than 2 decades. Nevertheless, that didn't stop Samantha from writing a memoir titled, "The Diary of Princess Pushy's Sister."

Unsurprisingly, Meghan's father Thomas also weighed in on Oprah's interview -- specifically Meghan's revelation of her mental health struggles -- claiming she might not have reached the point of feeling suicidal if she hadn't bailed on him and the fam.

Samantha has more thoughts on the broken relationship between Meghan and their dad, and what it would take to fix it.