When I write the phrase, "in all seriousness," I mean, as a completely serious, literal point, without sarcasm, irony, or humor.
Example: "In all seriousness, that house looks absolutely hideous. That shade of purple makes me want to cry."
This is saying, the house in question is not being described as hideous as some sort of joke; no, it really is hideous.
(A house in my local community, which was mercifully torn down to make room for a pharmacy a decade ago, fit this description perfectly, and was painful to even look at for many years. - Jeremiah)